15 research outputs found
ΠΠΈΠ³Π°Π½Π΄Ρ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΡ Π±Π΅Π»ΠΊΠΎΠ² ΠΡΠ°Ρ ΠΊΠ°ΠΊ ΠΈΠ½ΡΡΡΡΠΌΠ΅Π½ΡΡ Π΄Π»Ρ ΠΈΠ·ΡΡΠ΅Π½ΠΈΡ ΠΈΡ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈ ΡΠΎΠ·Π΄Π°Π½ΠΈΡ Π½ΠΎΠ²ΡΡ ΠΎΡΠΈΠ³ΠΈΠ½Π°Π»ΡΠ½ΡΡ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ ΡΡΠ΅Π΄ΡΡΠ²
The review discusses modern views about the structure and functions of Epac proteins (exchange proteins directly activated by cyclic adenosine monophosphate). The involvement of Epac proteins both in the regulation of the physiological functions of the body and in the initiation of various pathological processes allows to consider them as a fundamentally new biological target for creating original, highly effective drugs. Information on existing Epac protein agonists and antagonists was collected, and the influence of Epac ligands structure on the values of their affinity and selectivity was analyzed. Presumptive mechanisms of the interaction of ligands with Epac proteins are presented.Π ΠΎΠ±Π·ΠΎΡΠ΅ ΡΠ°ΡΡΠΌΠΎΡΡΠ΅Π½Ρ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΠ΅ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ΠΈΡ ΠΎ ΡΡΡΠΎΠ΅Π½ΠΈΠΈ ΠΈ ΡΡΠ½ΠΊΡΠΈΡΡ
Π±Π΅Π»ΠΊΠΎΠ² ΠΡΠ°Ρ (exchange proteins directly activated by cAMP, ΠΎΠ±ΠΌΠ΅Π½Π½ΡΠ΅ Π±Π΅Π»ΠΊΠΈ, Π½Π°ΠΏΡΡΠΌΡΡ Π°ΠΊΡΠΈΠ²ΠΈΡΡΠ΅ΠΌΡΠ΅ ΡΠΈΠΊΠ»ΠΈΡΠ΅ΡΠΊΠΈΠΌ Π°Π΄Π΅Π½ΠΎΠ·ΠΈΠ½ΠΌΠΎΠ½ΠΎΡΠΎΡΡΠ°ΡΠΎΠΌ). ΠΠΎΠ²Π»Π΅ΡΡΠ½Π½ΠΎΡΡΡ Π±Π΅Π»ΠΊΠΎΠ² ΠΡΠ°Ρ ΠΊΠ°ΠΊ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΡ ΡΠΈΠ·ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΡΠ½ΠΊΡΠΈΠΉ ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠ°, ΡΠ°ΠΊ ΠΈ Π² ΠΈΠ½ΠΈΡΠΈΠ°ΡΠΈΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΏΡΠΎΡΠ΅ΡΡΠΎΠ² ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΡΠ°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°ΡΡ ΠΈΡ
ΠΊΠ°ΠΊ ΠΏΡΠΈΠ½ΡΠΈΠΏΠΈΠ°Π»ΡΠ½ΠΎ Π½ΠΎΠ²ΡΡ Π±ΠΈΠΎΠΌΠΈΡΠ΅Π½Ρ Π΄Π»Ρ ΡΠΎΠ·Π΄Π°Π½ΠΈΡ ΠΎΡΠΈΠ³ΠΈΠ½Π°Π»ΡΠ½ΡΡ
, Π²ΡΡΠΎΠΊΠΎΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΡ
Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΡΡΠ΅Π΄ΡΡΠ². Π‘ΠΎΠ±ΡΠ°Π½Ρ ΡΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΎ ΡΡΡΠ΅ΡΡΠ²ΡΡΡΠΈΡ
Π°Π³ΠΎΠ½ΠΈΡΡΠ°Ρ
ΠΈ Π°Π½ΡΠ°Π³ΠΎΠ½ΠΈΡΡΠ°Ρ
Π±Π΅Π»ΠΊΠΎΠ² ΠΡΠ°Ρ, ΠΏΡΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡΠΎΠ²Π°Π½ΠΎ Π²Π»ΠΈΡΠ½ΠΈΠ΅ ΡΡΡΠΎΠ΅Π½ΠΈΡ Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ² ΠΡΠ°Ρ Π½Π° Π·Π½Π°ΡΠ΅Π½ΠΈΡ ΠΈΡ
Π°ΡΡΠΈΠ½Π½ΠΎΡΡΠΈ ΠΈ ΡΠ΅Π»Π΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ. ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Ρ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»Π°Π³Π°Π΅ΠΌΡΠ΅ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΡ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ² Ρ Π±Π΅Π»ΠΊΠ°ΠΌΠΈ ΠΡΠ°Ρ
ΠΡΠΈΡΡΡΡΠΉ Π΄Π»Ρ Π·Π°Π±ΠΎΡΡ Π²Π΅Π½ΠΎΠ·Π½ΠΎΡ ΠΊΡΠΎΠ²Ρ
ΠΡΠΈΡΡΡΡΠΉ Π½Π°Π»Π΅ΠΆΠΈΡΡ Π΄ΠΎ ΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΠΈ, Π° ΡΠ°ΠΌΠ΅ Π΄ΠΎ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΠΎΡ Π΄ΡΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ Ρ ΠΏΡΠΈΠ·Π½Π°ΡΠ΅Π½ΠΈΠΉ Π΄Π»Ρ ΠΏΠΎΠ»Π΅Π³ΡΠ΅Π½Π½Ρ ΠΏΡΠΎΡΠ΅Π΄ΡΡΠΈ Π·Π°Π±ΠΎΡΡ Π²Π΅Π½ΠΎΠ·Π½ΠΎΡ ΠΊΡΠΎΠ²Ρ Π΄ΠΎ Π²Π°ΠΊΡΡΠΌΠ½ΠΈΡ
ΠΏΡΠΎΠ±ΡΡΠΎΠΊ (ΠΠ) ΠΌΠ΅Π΄ΠΈΡΠ½ΠΈΠΌ ΠΏΠ΅ΡΡΠΎΠ½Π°Π»ΠΎΠΌ Π΄Π»Ρ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π½Ρ Π±ΡΠΎΡ
ΡΠΌΡΡΠ½ΠΈΡ
Π΄ΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½Ρ. ΠΡΠ΄ΠΎΠΌΠΈΠΉ ΠΏΡΠΈΡΡΡΡΠΉ Winged catheter introducer with pre-bent wings (ΠΊΠ°ΡΠ΅ΡΠ΅Ρ "ΠΠ΅ΡΠ΅Π»ΠΈΠΊ") (Pat. 5306253 US, ΠΠΠ Π61Π 5/178. Winged catheter introducer with pre-bent wings / Brimhall G.L.; Π·Π°ΡΠ²Π½ΠΈΠΊ ΡΠ° ΠΏΠ°ΡΠ΅Π½ΡΠΎΠ²Π»Π°ΡΠ½ΠΈΠΊ: Becton, Dickinson And Company - β us5306253A). ΠΡΠ½ ΡΠΊΠ»Π°Π΄Π°ΡΡΡΡΡ Π· ΠΊΠ°Π½ΡΠ»Ρ Π· ΠΏΡΠΎΠ±ΠΊΠΎΡ, Π³ΠΎΠ»ΠΊΠΈ Π΄Π»Ρ Π²Π΅Π½Π΅ΠΏΡΠ½ΠΊΡΡΡ ΡΠ° Π³Π½ΡΡΠΊΠΎΡ ΠΏΡΠΎΠ·ΠΎΡΠΎΡ ΡΡΡΠ±ΠΊΠΈ, ΡΠΊΠ° ΡΡ
Π·'ΡΠ΄Π½ΡΡ. ΠΠ°ΠΉΠ±ΡΠ»ΡΡ Π±Π»ΠΈΠ·ΡΠΊΠΈΠΌ Π΄ΠΎ Π·Π°ΠΏΡΠΎΠΏΠΎΠ½ΠΎΠ²Π°Π½ΠΎΠ³ΠΎ ΠΏΡΠΈΡΡΡΠΎΡ Ρ Blood collection tube closure for use with a needle holder (Pat. 6024710 US, ΠΠΠ Π61Π 5/00. Blood collection tube closure for use with a needle holder / Miller H.F; Π·Π°ΡΠ²Π½ΠΈΠΊ ΡΠ° ΠΏΠ°ΡΠ΅Π½ΡΠΎΠ²Π»Π°ΡΠ½ΠΈΠΊ: Becton Dickinson and Company β β us006024710A; Π·Π°ΡΠ²Π». 30.09.1998; ΠΎΠΏΡΠ±Π». 15.02.2000). ΠΡΠ½ ΡΠΊΠ»Π°Π΄Π°ΡΡΡΡΡ Π· Π³Π΅ΡΠΌΠ΅ΡΠΈΡΠ½ΠΎ Π·Π°ΠΊΡΠΈΡΠΎΡ Π³ΡΠΌΠΎΠ²ΠΎΡ ΠΏΡΠΎΠ±ΠΊΠΎΡ ΠΏΡΠΎΠ±ΡΡΠΊΠΈ, Π² ΡΠΊΡΠΉ ΡΡΠ²ΠΎΡΠ΅Π½ΠΎ Π½Π΅Π³Π°ΡΠΈΠ²Π½ΠΈΠΉ ΡΠΈΡΠΊ, ΡΡΠΈΠΌΠ°ΡΠ° Π΄Π»Ρ Π³ΠΎΠ»ΠΊΠΈ ΡΠ° Π΄Π²ΠΎΡΡΠΎΡΠΎΠ½Π½ΡΠΎΡ Π³ΠΎΠ»ΠΊΠΈ Π΄Π»Ρ ΠΎΡΡΠΈΠΌΠ°Π½Π½Ρ Π²Π΅Π½ΠΎΠ·Π½ΠΎΡ ΠΊΡΠΎΠ²Ρ. ΠΡΠΈ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π½Ρ Π²Π΅Π½Π΅ΠΏΡΠ½ΠΊΡΡΡ ΡΡΠ°Π½Π΄Π°ΡΡΠ½ΠΎΡ Π³ΠΎΠ»ΠΊΠΎΡ Π΄Π»Ρ ΠΠ ΡΠ°ΡΡΠΎ ΡΠΏΠΎΡΡΠ΅ΡΡΠ³Π°ΡΡΡΡΡ ΡΠ΅Ρ
Π½ΡΡΠ½Ρ ΡΡΡΠ΄Π½ΠΎΡΡ. ΡΡ
Π²ΠΈΠ½ΠΈΠΊΠ½Π΅Π½Π½Ρ ΠΏΠΎΠ²'ΡΠ·Π°Π½Π΅ Π· Π½Π΅ΠΌΠΎΠΆΠ»ΠΈΠ²ΡΡΡΡ ΠΎΡΡΠΈΠΌΠ°Π½Π½Ρ ΠΏΡΠ΄ΡΠ²Π΅ΡΠ΄ΠΆΠ΅Π½Π½Ρ ("ΠΊΡΠΎΠ² Ρ ΡΠΏΡΠΈΡΡ") Π»ΠΎΠΊΠ°Π»ΡΠ·Π°ΡΡΡ Π²ΡΡΡΡΡ Π³ΠΎΠ»ΠΊΠΈ Ρ ΠΏΡΠΎΡΠ²ΡΡΡ ΡΡΠ΄ΠΈΠ½ΠΈ ΠΏΡΠΈ ΠΏΡΠ½ΠΊΡΡΡ Π²Π΅Π½, ΡΠΎ ΠΏΠΎΠ³Π°Π½ΠΎ Π²ΡΠ·ΡΠ°Π»ΡΠ·ΡΡΡΡΡΡ Π°Π±ΠΎ ΠΌΠ°ΡΡΡ ΠΌΠ°Π»ΠΈΠΉ Π΄ΡΠ°ΠΌΠ΅ΡΡ, Π°Π΄ΠΆΠ΅ ΠΏΡΠΈ ΠΎΡΡΠΈΠΌΠ°Π½Π½Ρ Π·ΡΠ°Π·ΠΊΡ ΠΊΡΠΎΠ²Ρ Π·Π° Π΄ΠΎΠΏΠΎΠΌΠΎΠ³ΠΎΡ ΠΠ, Π²ΠΎΠ½Π° ΠΌΠΎΠΆΠ΅ Π±ΡΡΠΈ ΠΏΡΠΈΡΠ΄Π½Π°Π½Π° Π΄ΠΎ Π³ΠΎΠ»ΠΊΠΈ Π»ΠΈΡΠ΅ ΠΏΡΡΠ»Ρ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π½Ρ Π²Π΅Π½Π΅ΠΏΡΠ½ΠΊΡΡΡ. ΠΡΡΠΌ ΡΠΎΠ³ΠΎ, ΠΠ, Π³ΡΠΌΠΎΠ²Π° ΠΏΡΠΎΠ±ΠΊΠ° ΡΠΊΠΎΡ Π±ΡΠ»Π° ΠΏΠ΅ΡΡΠΎΡΠΎΠ²Π°Π½Π° Π³ΠΎΠ»ΠΊΠΎΡ Π²ΠΆΠ΅ Π½Π΅ ΠΏΡΠ΄Π»ΡΠ³Π°Ρ ΠΏΠΎΠ²ΡΠΎΡΠ½ΠΎΠΌΡ Π²ΠΈΠΊΠΎΡΠΈΡΡΠ°Π½Π½Ρ Π½Π°Π²ΡΡΡ Ρ ΡΠ°Π·Ρ Π²ΡΠ΄ΡΡΡΠ½ΠΎΡΡΡ ΠΏΠΎΡΡΠ°ΠΏΠ»ΡΠ½Π½Ρ Π΄ΠΎ Π½Π΅Ρ ΠΊΡΠΎΠ²Ρ. Π ΠΎΡΠ½ΠΎΠ²Ρ ΠΊΠΎΡΠΈΡΠ½ΠΎΡ ΠΌΠΎΠ΄Π΅Π»Ρ ΠΏΠΎΡΡΠ°Π²Π»Π΅Π½ΠΎ Π·Π°Π΄Π°ΡΡ ΡΠ΄ΠΎΡΠΊΠΎΠ½Π°Π»ΠΈΡΠΈ ΠΏΡΠΈΡΡΡΡΠΉ Π΄Π»Ρ ΠΎΡΡΠΈΠΌΠ°Π½Π½Ρ Π·ΡΠ°Π·ΠΊΡΠ² Π²Π΅Π½ΠΎΠ·Π½ΠΎΡ ΠΊΡΠΎΠ²Ρ Π΄ΠΎ Π²Π°ΠΊΡΡΠΌΠ½ΠΈΡ
ΠΏΡΠΎΠ±ΡΡΠΎΠΊ. ΠΠΎΡΡΠ°Π²Π»Π΅Π½Π° Π·Π°Π΄Π°ΡΠ° Π²ΠΈΡΡΡΡΡΡΡΡΡ ΡΡΠ²ΠΎΡΠ΅Π½Π½ΡΠΌ ΠΏΡΠΈΡΡΡΠΎΡ Π΄Π»Ρ Π·Π°Π±ΠΎΡΡ Π²Π΅Π½ΠΎΠ·Π½ΠΎΡ ΠΊΡΠΎΠ²Ρ, ΡΠΊΠΈΠΉ ΡΠΊΠ»Π°Π΄Π°ΡΡΡΡΡ Π· Π³Π΅ΡΠΌΠ΅ΡΠΈΡΠ½ΠΎ Π·Π°ΠΊΡΠΈΡΠΎΡ Π³ΡΠΌΠΎΠ²ΠΎΡ ΠΏΡΠΎΠ±ΠΊΠΎΡ ΠΏΡΠΎΠ±ΡΡΠΊΠΈ, Π² ΡΠΊΡΠΉ ΡΡΠ²ΠΎΡΠ΅Π½ΠΎ Π½Π΅Π³Π°ΡΠΈΠ²Π½ΠΈΠΉ ΡΠΈΡΠΊ, ΡΡΠΈΠΌΠ°ΡΠ° Π΄Π»Ρ Π³ΠΎΠ»ΠΊΠΈ ΡΠ° ΡΡΠ°Π½Π΄Π°ΡΡΠ½ΠΎΡ Π³ΠΎΠ»ΠΊΠΈ Π΄Π»Ρ Π²Π°ΠΊΡΡΠΌΠ½ΠΈΡ
ΠΏΡΠΎΠ±ΡΡΠΎΠΊ Ρ Π²ΡΠ΄ΡΡΠ·Π½ΡΡΡΡΡΡ ΡΠΈΠΌ, ΡΠΎ ΡΡΠ°Π½Π΄Π°ΡΡΠ½Ρ Π³ΠΎΠ»ΠΊΡ Π΄Π»Ρ Π²Π°ΠΊΡΡΠΌΠ½ΠΈΡ
ΠΏΡΠΎΠ±ΡΡΠΎΠΊ Π·'ΡΠ΄Π½Π°Π½ΠΎ Π· ΠΏΡΠΎΠΊΡΠΈΠΌΠ°Π»ΡΠ½ΠΈΠΌ ΠΊΡΠ½ΡΠ΅ΠΌ ΠΊΠ°ΡΠ΅ΡΠ΅ΡΠ° "ΠΠ΅ΡΠ΅Π»ΠΈΠΊ". ΠΠΈΠΊΠΎΡΠΈΡΡΠ°Π½Π½Ρ Π΄Π°Π½ΠΎΠ³ΠΎ ΠΏΡΠΈΡΡΡΠΎΡ Π΄ΠΎΠ·Π²ΠΎΠ»ΡΡ ΡΠΎΠ·Π²'ΡΠ·Π°ΡΠΈ ΡΠ΅Ρ
Π½ΡΡΠ½Π΅ Π·Π°Π²Π΄Π°Π½Π½Ρ, ΡΠΎ ΠΏΠΎΠ»ΡΠ³Π°Ρ Ρ Π½Π΅ΠΎΠ±Ρ
ΡΠ΄Π½ΠΎΡΡΡ Π²ΠΈΠ·Π½Π°ΡΠ΅Π½Π½Ρ ΠΌΠΎΠΌΠ΅Π½ΡΡ ΠΏΠΎΡΡΠ°ΠΏΠ»ΡΠ½Π½Ρ Π²ΡΡΡΡΡ Π³ΠΎΠ»ΠΊΠΈ Π΄ΠΎ ΠΏΡΠΎΡΠ²ΡΡΡ ΡΡΠ΄ΠΈΠ½ΠΈ. ΠΡΠΈΡΡΡΡΠΉ Π·Π°ΡΡΠΎΡΠΎΠ²ΡΡΡΡΡΡ Π½Π°ΡΡΡΠΏΠ½ΠΈΠΌ ΡΠΈΠ½ΠΎΠΌ. ΠΠ΅ΡΠ΅Π΄ Π²Π΅Π½Π΅ΠΏΡΠ½ΠΊΡΡΡΡ ΡΡΠ°Π½Π΄Π°ΡΡΠ½ΠΎΡ Π³ΠΎΠ»ΠΊΠΎΡ Π΄Π»Ρ ΠΠ ΠΏΡΠΎΠΊΠΎΠ»ΡΡΡΡ ΠΊΡΠΈΡΠΊΡ ΠΏΠΎΡΡΡ ΠΊΠ°ΡΠ΅ΡΠ΅ΡΠ° "ΠΠ΅ΡΠ΅Π»ΠΈΠΊ" 1. ΠΡΡΠ»Ρ ΡΡΠΎΠ³ΠΎ Π² ΠΏΡΠΎΡΠ΅ΡΡ 30 ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π½Ρ ΠΏΡΠ½ΠΊΡΡΡ Π·Π° Π΄ΠΎΠΏΠΎΠΌΠΎΠ³ΠΎΡ ΡΠΎΠ·ΡΠΎΠ±Π»Π΅Π½ΠΎΠ³ΠΎ ΠΏΡΠΈΡΡΡΠΎΡ ΠΌΠΎΠΌΠ΅Π½Ρ ΠΏΠΎΡΡΠ°ΠΏΠ»ΡΠ½Π½Ρ Π³ΠΎΠ»ΠΊΠΈ ΠΊΠ°ΡΠ΅ΡΠ΅ΡΠ° "ΠΠ΅ΡΠ΅Π»ΠΈΠΊ" Π΄ΠΎ ΠΏΡΠΎΡΠ²ΡΡΡ Π²Π΅Π½ΠΈ ΠΌΠΎΠΆΠ½Π° ΡΡΡΠΊΠΎ Π²ΡΠ΄ΡΡΠ΅ΠΆΠΈΡΠΈ ΡΠ»ΡΡ
ΠΎΠΌ Π²ΡΠ·ΡΠ°Π»ΡΠ½ΠΎΡ ΡΠ΅ΡΡΡΡΠ°ΡΡΡ ΠΏΠΎΡΠ²ΠΈ ΠΊΡΠΎΠ²Ρ Ρ ΠΏΡΠΎΡΠ²ΡΡΡ Π³Π½ΡΡΠΊΠΎΡ ΡΡΡΠ±ΠΊΠΈ ΠΊΠ°ΡΠ΅ΡΠ΅ΡΠ°. ΠΠ°ΡΡΠΎΡΡΠ²Π°Π½Π½Ρ Π·Π°ΠΏΡΠΎΠΏΠΎΠ½ΠΎΠ²Π°Π½ΠΎΠ³ΠΎ ΠΏΡΠΈΡΡΡΠΎΡ ΠΏΠΎΠ»Π΅Π³ΡΡΡ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π½Ρ ΡΠ΅Ρ
Π½ΡΡΠ½ΠΎ ΡΠΊΠ»Π°Π΄Π½ΠΎΡ Π²Π΅Π½Π΅ΠΏΡΠ½ΠΊΡΡΡ, ΡΠΎ Π΄ΠΎΠ·Π²ΠΎΠ»ΡΡ Π·Π½ΠΈΠ·ΠΈΡΠΈ ΡΡΡΠΏΡΠ½Ρ ΠΌΠ΅Ρ
Π°Π½ΡΡΠ½ΠΎΡ ΡΡΠ°Π²ΠΌΠ°ΡΠΈΠ·Π°ΡΡΡ ΠΌ'ΡΠΊΠΈΡ
ΡΠΊΠ°Π½ΠΈΠ½ ΡΠ° Π²Π΅Π½ΠΎΠ·Π½ΠΎΡ ΡΡΡΠ½ΠΊΠΈ ΠΏΠ°ΡΡΡΠ½ΡΠ° ΡΠ° Π·ΠΌΠ΅Π½ΡΠΈΡΠΈ ΠΊΡΠ»ΡΠΊΡΡΡΡ Π·ΡΠΏΡΠΎΠ²Π°Π½ΠΈΡ
Π
ΠΠ»ΠΈΡΠ½ΠΈΠ΅ ΡΠ°Π±ΠΎΠΌΠΎΡΠΈΠ·ΠΎΠ»Π° Π½Π° ΠΌΠΈΠΊΡΠΎΡΠΈΡΠΊΡΠ»ΡΡΠΈΡ ΠΊΡΠΎΠ²ΠΈ Π² ΠΈΠ½ΡΠ°ΠΊΡΠ½ΠΎΠΌ ΠΈ ΠΈΡΠ΅ΠΌΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΌ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π΅
The investigation purpose was to study the effect of fabomotizole on blood microcirculation in intact and ischemic myocardium in conditions of acute ischemia of the heart muscle. The experiments were carried out on anesthetized (urethane, 1300 mg/kg, i.p.) white mongrel male rats weighing 220β250 g. Acute myocardial ischemia was caused by occlusion of the left coronary artery. Blood microcirculation was evaluated by laser Doppler flowmetry using a computerized laser analyzer "LAKK-OP2". It was found that fabomotizole (15 mg/kg, i.v.) in an intact heart does not affect blood microcirculation. Immediately after coronary artery ligation in the myocardial ischemia zone, microcirculation decreases sharply (by about 30 %, p = 0.0106) and practically does not change in the conditionally intact myocardium. Fabomotizole, administered 5 minutes before occlusion of the coronary artery, prevented a decrease in microcirculation in the ischemiΡ zone of the myocardium. The ability of fabomotizole in conditions of acute myocardial ischemia to prevent a decrease in the level of microcirculation in the ischemic zone may contribute to the anti-ischemic activity of the drug.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ β ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π²Π»ΠΈΡΠ½ΠΈΡ ΡΠ°Π±ΠΎΠΌΠΎΡΠΈΠ·ΠΎΠ»Π° Π½Π° ΠΌΠΈΠΊΡΠΎΡΠΈΡΠΊΡΠ»ΡΡΠΈΡ ΠΊΡΠΎΠ²ΠΈ Π² ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π΅ Π² ΡΡΠ»ΠΎΠ²ΠΈΡΡ
ΠΎΡΡΡΠΎΠΉ ΠΈΡΠ΅ΠΌΠΈΠΈ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎΠΉ ΠΌΡΡΡΡ. ΠΠΏΡΡΡ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ Π½Π° Π½Π°ΡΠΊΠΎΡΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
(ΡΡΠ΅ΡΠ°Π½, 1300 ΠΌΠ³/ΠΊΠ³ Π²/Π±) Π±Π΅Π»ΡΡ
Π±Π΅ΡΠΏΠΎΡΠΎΠ΄Π½ΡΡ
ΠΊΡΡΡΠ°Ρ
-ΡΠ°ΠΌΡΠ°Ρ
ΠΌΠ°ΡΡΠΎΠΉ 220β250 Π³. ΠΡΡΡΡΡ ΠΈΡΠ΅ΠΌΠΈΡ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π° Π²ΡΠ·ΡΠ²Π°Π»ΠΈ ΠΎΠΊΠΊΠ»ΡΠ·ΠΈΠ΅ΠΉ Π»Π΅Π²ΠΎΠΉ ΠΊΠΎΡΠΎΠ½Π°ΡΠ½ΠΎΠΉ Π°ΡΡΠ΅ΡΠΈΠΈ. ΠΠΈΠΊΡΠΎΡΠΈΠΊΡΠ»ΡΡΠΈΡ ΠΊΡΠΎΠ²ΠΈ ΠΎΡΠ΅Π½ΠΈΠ²Π°Π»ΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ Π»Π°Π·Π΅ΡΠ½ΠΎΠΉ Π΄ΠΎΠΏΠΏΠ»Π΅ΡΠΎΠ²ΡΠΊΠΎΠΉ ΡΠ»ΠΎΡΠΌΠ΅ΡΡΠΈΠΈ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΊΠΎΠΌΠΏΡΡΡΠ΅ΡΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ Π»Π°Π·Π΅ΡΠ½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π°ΡΠΎΡΠ° Β«ΠΠΠΠ-ΠΠ2Β». Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ ΡΠ°Π±ΠΎΠΌΠΎΡΠΈΠ·ΠΎΠ» (15 ΠΌΠ³/ΠΊΠ³, Π²/Π²) Π² ΠΈΠ½ΡΠ°ΠΊΡΠ½ΠΎΠΌ ΡΠ΅ΡΠ΄ΡΠ΅ Π½Π΅ Π²Π»ΠΈΡΠ΅Ρ Π½Π° ΠΌΠΈΠΊΡΠΎΡΠΈΡΠΊΡΠ»ΡΡΠΈΡ ΠΊΡΠΎΠ²ΠΈ. Π‘ΡΠ°Π·Ρ ΠΆΠ΅ ΠΏΠΎΡΠ»Π΅ ΠΏΠ΅ΡΠ΅Π²ΡΠ·ΠΊΠΈ ΠΊΠΎΡΠΎΠ½Π°ΡΠ½ΠΎΠΉ Π°ΡΡΠ΅ΡΠΈΠΈ Π² Π·ΠΎΠ½Π΅ ΠΈΡΠ΅ΠΌΠΈΠΈ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π° ΠΌΠΈΠΊΡΠΎΡΠΈΡΠΊΡΠ»ΡΡΠΈΡ ΡΠ΅Π·ΠΊΠΎ ΡΠΌΠ΅Π½ΡΡΠ°Π΅ΡΡΡ (ΠΏΡΠΈΠΌΠ΅ΡΠ½ΠΎ Π½Π° 30 %, Ρ = 0,0106) ΠΈ ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΈ Π½Π΅ ΠΌΠ΅Π½ΡΠ΅ΡΡΡ Π² ΡΡΠ»ΠΎΠ²Π½ΠΎ-ΠΈΠ½ΡΠ°ΠΊΡΠ½ΠΎΠΌ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π΅. Π€Π°Π±ΠΎΠΌΠΎΡΠΈΠ·ΠΎΠ», Π²Π²Π΅Π΄ΡΠ½Π½ΡΠΉ Π·Π° 5 ΠΌΠΈΠ½ Π΄ΠΎ ΠΎΠΊΠΊΠ»ΡΠ·ΠΈΠΈ ΠΊΠΎΡΠΎΠ½Π°ΡΠ½ΠΎΠΉ Π°ΡΡΠ΅ΡΠΈΠΈ, ΠΏΡΠ΅Π΄ΠΎΡΠ²ΡΠ°ΡΠ°Π» ΡΠΌΠ΅Π½ΡΡΠ΅Π½ΠΈΠ΅ ΠΌΠΈΠΊΡΠΎΡΠΈΡΠΊΡΠ»ΡΡΠΈΠΈ Π² Π·ΠΎΠ½Π΅ ΠΈΡΠ΅ΠΌΠΈΠΈ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π°. Π‘ΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΡ ΡΠ°Π±ΠΎΠΌΠΎΡΠΈΠ·ΠΎΠ»Π° Π² ΡΡΠ»ΠΎΠ²ΠΈΡΡ
ΠΎΡΡΡΠΎΠΉ ΠΈΡΠ΅ΠΌΠΈΠΈ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π° ΠΏΡΠ΅ΠΏΡΡΡΡΠ²ΠΎΠ²Π°ΡΡ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΡ ΡΡΠΎΠ²Π½Ρ ΠΌΠΈΠΊΡΠΎΡΠΈΡΠΊΡΠ»ΡΡΠΈΠΈ Π² ΠΈΡΠ΅ΠΌΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ Π·ΠΎΠ½Π΅ ΠΌΠΎΠΆΠ΅Ρ Π²Π½ΠΎΡΠΈΡΡ Π²ΠΊΠ»Π°Π΄ Π² ΠΏΡΠΎΡΠΈΠ²ΠΎΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°
Π Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠΈ Π²ΡΡΠ²Π»Π΅Π½ΠΈΡ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° Β«ΠΊΠΎΡΠΎΠ½Π°ΡΠ½ΠΎΠ³ΠΎ ΠΎΠ±ΠΊΡΠ°Π΄ΡΠ²Π°Π½ΠΈΡΒ» Π½Π° ΠΌΠ΅Π»ΠΊΠΈΡ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΡΡ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ
The purpose of the study. There are investigation of the possibility of using the laser Doppler flowmetry method to assess blood microcirculation and analyze the mechanisms of its regulation in conditionally intact and ischemic myocardium in small laboratory animals (rats) to identify the "coronary theft" syndrome. Materials and methods. The experiments were carried out on white mongrel anesthetized (urethane 1300 mg/kg /b) male rats weighing 200-250 g. 28 days after the reproduction of an experimental myocardial infarction in an open chest and artificial lung ventilation, the microcirculation level was assessed in conditionally intact and ischemic areas of the myocardium by laser Doppler flowmetry. Using spectral wavelet analysis, the amplitudes of microcirculation oscillations normalized to the total perfusion associated with various regulation mechanisms were determined. Results. It was found that the microcirculation level is significantly lower in the ischemic zone of the myocardium compared with the conditionally intact one (17.3Β±2.8 and 30.3Β±1.3 per. units, respectively, p = 0.006, n = 8). Spectral wavelet analysis showed that in the ischemic injury zone, in comparison with the conditionally intact myocardium, the amplitudes of microcirculation oscillations normalized to the general level of microcirculation increase for all regulatory mechanisms. Conclusion. The laser Doppler flowmetry method can be used to assess the intensity of microcirculation in conditionally intact and ischemic myocardium. Using this method makes it possible to identify the "coronary theft" syndrome in experiments on small experimental animals.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ. ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠΈ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ ΠΌΠ΅ΡΠΎΠ΄Π° Π»Π°Π·Π΅ΡΠ½ΠΎΠΉ Π΄ΠΎΠΏΠΏΠ»Π΅ΡΠΎΠ²ΡΠΊΠΎΠΉ ΡΠ»ΠΎΡΠΌΠ΅ΡΡΠΈΠΈ Π΄Π»Ρ ΠΎΡΠ΅Π½ΠΊΠΈ ΠΌΠΈΠΊΡΠΎΡΠΈΡΠΊΡΠ»ΡΡΠΈΠΈ ΠΊΡΠΎΠ²ΠΈ ΠΈ Π°Π½Π°Π»ΠΈΠ·Π° ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΎΠ² Π΅Ρ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ Π² ΡΡΠ»ΠΎΠ²Π½ΠΎ-ΠΈΠ½ΡΠ°ΠΊΡΠ½ΠΎΠΌ ΠΈ ΠΈΡΠ΅ΠΌΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΌ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π΅ Ρ ΠΌΠ΅Π»ΠΊΠΈΡ
Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΡΡ
ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ
(ΠΊΡΡΡ) Π΄Π»Ρ ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° Β«ΠΊΠΎΡΠΎΠ½Π°ΡΠ½ΠΎΠ³ΠΎ ΠΎΠ±ΠΊΡΠ°Π΄ΡΠ²Π°Π½ΠΈΡΒ». ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΠΏΡΡΡ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ Π½Π° Π±Π΅Π»ΡΡ
Π±Π΅ΡΠΏΠΎΡΠΎΠ΄Π½ΡΡ
Π½Π°ΡΠΊΠΎΡΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
(ΡΡΠ΅ΡΠ°Π½ 1300 ΠΌΠ³/ΠΊΠ³ Π²/Π±) ΠΊΡΡΡΠ°Ρ
-ΡΠ°ΠΌΡΠ°Ρ
ΠΌΠ°ΡΡΠΎΠΉ 200β250 Π³. Π§Π΅ΡΠ΅Π· 28 ΡΡΡΠΎΠΊ ΠΏΠΎΡΠ»Π΅ Π²ΠΎΡΠΏΡΠΎΠΈΠ·Π²Π΅Π΄Π΅Π½ΠΈΡ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΈΠ½ΡΠ°ΡΠΊΡΠ° ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π° Π² ΡΡΠ»ΠΎΠ²ΠΈΡΡ
ΠΎΡΠΊΡΡΡΠΎΠΉ Π³ΡΡΠ΄Π½ΠΎΠΉ ΠΊΠ»Π΅ΡΠΊΠΈ ΠΈ ΠΈΡΠΊΡΡΡΡΠ²Π΅Π½Π½ΠΎΠΉ Π²Π΅Π½ΡΠΈΠ»ΡΡΠΈΠΈ Π»ΡΠ³ΠΊΠΈΡ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ Π»Π°Π·Π΅ΡΠ½ΠΎΠΉ Π΄ΠΎΠΏΠΏΠ»Π΅ΡΠΎΠ²ΡΠΊΠΎΠΉ ΡΠ»ΠΎΡΠΌΠ΅ΡΡΠΈΠΈ ΠΎΡΠ΅Π½ΠΈΠ²Π°Π»ΠΈ ΡΡΠΎΠ²Π΅Π½Ρ ΠΌΠΈΠΊΡΠΎΡΠΈΡΠΊΡΠ»ΡΡΠΈΠΈ Π² ΡΡΠ»ΠΎΠ²Π½ΠΎ-ΠΈΠ½ΡΠ°ΠΊΡΠ½ΠΎΠΉ ΠΈ ΠΈΡΠ΅ΠΌΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ Π·ΠΎΠ½Π°Ρ
ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π°. ΠΡΠΏΠΎΠ»ΡΠ·ΡΡ ΡΠΏΠ΅ΠΊΡΡΠ°Π»ΡΠ½ΡΠΉ Π²Π΅ΠΉΠ²Π»Π΅Ρ Π°Π½Π°Π»ΠΈΠ·, ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ Π½ΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΊ ΠΎΠ±ΡΠ΅ΠΉ ΠΏΠ΅ΡΡΡΠ·ΠΈΠΈ Π°ΠΌΠΏΠ»ΠΈΡΡΠ΄ ΠΎΡΡΠΈΠ»Π»ΡΡΠΈΠΉ ΠΌΠΈΠΊΡΠΎΠΊΡΠΎΠ²ΠΎΡΠΎΠΊΠ°, ΡΠ²ΡΠ·Π°Π½Π½ΡΡ
Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠΌΠΈ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠ°ΠΌΠΈ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Ρ ΠΌΠΈΠΊΡΠΎΡΠΈΡΠΊΡΠ»ΡΡΠΈΠΈ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎ Π½ΠΈΠΆΠ΅ Π² ΠΈΡΠ΅ΠΌΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ Π·ΠΎΠ½Π΅ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π° ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ ΡΡΠ»ΠΎΠ²Π½ΠΎ-ΠΈΠ½ΡΠ°ΠΊΡΠ½ΠΎΠΉ (17,3Β±2,8 ΠΈ 30,3Β±1,3 ΠΏΠ΅Ρ. Π΅Π΄., ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ, p = 0,006, n = 8). Π‘ΠΏΠ΅ΠΊΡΡΠ°Π»ΡΠ½ΡΠΉ Π²Π΅ΠΉΠ²Π»Π΅Ρ Π°Π½Π°Π»ΠΈΠ· ΠΏΠΎΠΊΠ°Π·Π°Π», ΡΡΠΎ Π² Π·ΠΎΠ½Π΅ ΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΏΠΎΠ²ΡΠ΅ΠΆΠ΄Π΅Π½ΠΈΡ, ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ ΡΡΠ»ΠΎΠ²Π½ΠΎ-ΠΈΠ½ΡΠ°ΠΊΡΠ½ΡΠΌ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄ΠΎΠΌ, Π°ΠΌΠΏΠ»ΠΈΡΡΠ΄Ρ ΠΎΡΡΠΈΠ»Π»ΡΡΠΈΠΉ ΠΌΠΈΠΊΡΠΎΠΊΡΠΎΠ²ΠΎΡΠΎΠΊΠ°, Π½ΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ Π½Π° ΠΎΠ±ΡΠΈΠΉ ΡΡΠΎΠ²Π΅Π½Ρ ΠΌΠΈΠΊΡΠΎΡΠΈΡΠΊΡΠ»ΡΡΠΈΠΈ, ΡΠ²Π΅Π»ΠΈΡΠΈΠ²Π°ΡΡΡΡ Π΄Π»Ρ Π²ΡΠ΅Ρ
ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠΎΠ² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ. ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠ΅ΡΠΎΠ΄ Π»Π°Π·Π΅ΡΠ½ΠΎΠΉ Π΄ΠΎΠΏΠΏΠ»Π΅ΡΠΎΠ²ΡΠΊΠΎΠΉ ΡΠ»ΠΎΡΠΌΠ΅ΡΡΠΈΠΈ ΠΌΠΎΠΆΠ΅Ρ Π±ΡΡΡ ΠΏΡΠΈΠΌΠ΅Π½ΡΠ½ Π΄Π»Ρ ΠΎΡΠ΅Π½ΠΊΠΈ ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΌΠΈΠΊΡΠΎΡΠΈΡΠΊΡΠ»ΡΡΠΈΠΈ Π² ΡΡΠ»ΠΎΠ²Π½ΠΎ-ΠΈΠ½ΡΠ°ΠΊΡΠ½ΠΎΠΌ ΠΈ ΠΈΡΠ΅ΠΌΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΌ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π΅. ΠΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΡΠΎΠ³ΠΎ ΠΌΠ΅ΡΠΎΠ΄Π° Π΄Π°ΡΡ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ Π² ΠΎΠΏΡΡΠ°Ρ
Π½Π° ΠΌΠ΅Π»ΠΊΠΈΡ
ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΡΡ
ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ
Π²ΡΡΠ²ΠΈΡΡ ΡΠΈΠ½Π΄ΡΠΎΠΌ Β«ΠΊΠΎΡΠΎΠ½Π°ΡΠ½ΠΎΠ³ΠΎ ΠΎΠ±ΠΊΡΠ°Π΄ΡΠ²Π°Π½ΠΈΡΒ».
ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π²Π»ΠΈΡΠ½ΠΈΡ Π±Π»ΠΎΠΊΠ°Π΄Ρ VEGF ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² Π½Π° Π°Π½ΡΠΈΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΠ-2 Π½Π° ΠΌΠΎΠ΄Π΅Π»ΠΈ ΠΈΡΠ΅ΠΌΠΈΠΈ Π·Π°Π΄Π½Π΅ΠΉ ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΡΡΠΈ ΠΊΡΡΡ
Earlier, in experiments in vitro and in vivo, it was shown that the TrkA receptor agonist compound GK-2, which was a low molecular weight NGF mimetic, had pronounced angiogenic and antiischemic activity. However, it remained unclear whether this activity was associated with the activation of VEGF-A, since, on the one hand, there are reports that NGF-mediated angiogenesis can be initiated by activating NGF of the vascular endothelial growth factor VEGF-A, and on the other hand, it is shown that a selective antagonist of Flk1 receptors specific for VEGF-A, compound SU-5416 does not affect the angiogenic effect of NGF. Purpose of the investigation. Study of the selective VEGF blockade effect on the antiischemic activity of the TrkA receptor agonist GK-2. Methods. Evaluation of the compound GK-2 antiischemic activity was assessed in model experiments simulating hind limb ischemia in rats. Results. It has been shown that against the background of blockade of VEGF-A binding with specific for it (VEGFR1 / Flt-1 / and VEGFR2 / KDR /) receptors, bevacizumab (2.5 mg / kg, i.p., every 3 days for 14 days) compound GK-2 (1 mg / kg, i.p., daily, for 14 days) realizes its antiischemic activity. Conclusion. The results of these experiments indicate that the selective blockade of VEGF does not significantly affect the anti-ischemic activity of the dipeptide NGF mimetic compound GK-2, which has the properties of a TrkA receptor agonist.Π Π°Π½Π΅Π΅ Π² ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Ρ
in vitro ΠΈ in vivo Π±ΡΠ»ΠΎ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Π°Π³ΠΎΠ½ΠΈΡΡ TrkA-ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅ ΠΠ-2, ΡΠ²Π»ΡΡΡΠ΅Π΅ΡΡ Π½ΠΈΠ·ΠΊΠΎΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΠΌ ΠΌΠΈΠΌΠ΅ΡΠΈΠΊΠΎΠΌ NGF, ΠΎΠ±Π»Π°Π΄Π°Π΅Ρ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΠΎΠΉ Π°Π½Π³ΠΈΠΎΠ³Π΅Π½Π½ΠΎΠΉ ΠΈ Π°Π½ΡΠΈΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡΡ. ΠΠ΄Π½Π°ΠΊΠΎ ΠΎΡΡΠ°Π²Π°Π»ΠΎΡΡ Π½Π΅ ΡΡΠ½ΡΠΌ, ΡΠ²ΡΠ·Π°Π½Π° Π»ΠΈ ΡΡΠ° Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Ρ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠ΅ΠΉ VEGF-Π, ΠΏΠΎΡΠΊΠΎΠ»ΡΠΊΡ, Ρ ΠΎΠ΄Π½ΠΎΠΉ ΡΡΠΎΡΠΎΠ½Ρ, ΠΈΠΌΠ΅ΡΡΡΡ ΡΠΎΠΎΠ±ΡΠ΅Π½ΠΈΡ ΠΎ ΡΠΎΠΌ, ΡΡΠΎ NGF-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΡΠΉ Π°Π½Π³ΠΈΠΎΠ³Π΅Π½Π΅Π· ΠΌΠΎΠΆΠ΅Ρ Π±ΡΡΡ ΠΈΠ½ΠΈΡΠΈΠΈΡΠΎΠ²Π°Π½ ΠΈ ΠΏΡΡΡΠΌ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠΈ NGF ΡΠ°ΠΊΡΠΎΡΠ° ΡΠΎΡΡΠ° ΡΠ½Π΄ΠΎΡΠ΅Π»ΠΈΡ ΡΠΎΡΡΠ΄ΠΎΠ² VEGF-A, Π° Ρ Π΄ΡΡΠ³ΠΎΠΉ ΡΡΠΎΡΠΎΠ½Ρ, Π±ΡΠ»ΠΎ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ ΡΠ΅Π»Π΅ΠΊΡΠΈΠ²Π½ΡΠΉ Π°Π½ΡΠ°Π³ΠΎΠ½ΠΈΡΡ Flk1 ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ², ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΡΡ
Π΄Π»Ρ VEGF-A, ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅ SU-5416 Π½Π΅ Π²Π»ΠΈΡΠ΅Ρ Π½Π° Π°Π½Π³ΠΈΠΎΠ³Π΅Π½Π½ΡΠΉ ΡΡΡΠ΅ΠΊΡ NGF. Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ. ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π²Π»ΠΈΡΠ½ΠΈΡ ΡΠ΅Π»Π΅ΠΊΡΠΈΠ²Π½ΠΎΠΉ Π±Π»ΠΎΠΊΠ°Π΄Ρ VEGF Π½Π° Π°Π½ΡΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π°Π³ΠΎΠ½ΠΈΡΡΠ° TrkA ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΠ-2. ΠΠ΅ΡΠΎΠ΄Ρ. ΠΡΠ΅Π½ΠΊΡ Π°Π½ΡΠΈΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΠ-2 ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ Π² ΠΌΠΎΠ΄Π΅Π»ΡΠ½ΡΡ
ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Ρ
, Π²ΠΎΡΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΡΡΠΈΡ
ΠΈΡΠ΅ΠΌΠΈΡ Π·Π°Π΄Π½Π΅ΠΉ ΠΊΠΎΠ½Π΅ΡΠ½ΠΎΡΡΠΈ Ρ ΠΊΡΡΡ. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Π½Π° ΡΠΎΠ½Π΅ Π±Π»ΠΎΠΊΠ°Π΄Ρ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ VEGF-A ΡΠΎ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΡΠΌΠΈ Π΄Π»Ρ Π½Π΅Π³ΠΎ (VEGFR1 /Flt-1/ ΠΈ VEGFR2 /KDR/) ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°ΠΌΠΈ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠΌ Π±Π΅Π²Π°ΡΠΈΠ·ΡΠΌΠ°Π± (2,5 ΠΌΠ³/ΠΊΠ³, Π²/Π±, ΠΊΠ°ΠΆΠ΄ΡΠ΅ 3 Π΄Π½Ρ Π½Π° ΠΏΡΠΎΡΡΠΆΠ΅Π½ΠΈΠ΅ 14 Π΄Π½Π΅ΠΉ) ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅ ΠΠ-2 (1 ΠΌΠ³/ΠΊΠ³, Π²/Π±, Π΅ΠΆΠ΅Π΄Π½Π΅Π²Π½ΠΎ, Π² ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ 14 Π΄Π½Π΅ΠΉ) ΡΠ΅Π°Π»ΠΈΠ·ΡΠ΅Ρ ΡΠ²ΠΎΡ Π°Π½ΡΠΈΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ. ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ Π½Π°ΡΡΠΎΡΡΠΈΡ
ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠΎΠ² ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡΡ ΠΎ ΡΠΎΠΌ, ΡΡΠΎ ΡΠ΅Π»Π΅ΠΊΡΠΈΠ²Π½Π°Ρ Π±Π»ΠΎΠΊΠ°Π΄Π° VEGF Π½Π΅ ΠΎΠΊΠ°Π·ΡΠ²Π°Π΅Ρ ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ Π²Π»ΠΈΡΠ½ΠΈΡ Π½Π° ΠΏΡΠΎΡΠΈΠ²ΠΎΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π΄ΠΈΠΏΠ΅ΠΏΡΠΈΠ΄Π½ΠΎΠ³ΠΎ ΠΌΠΈΠΌΠ΅ΡΠΈΠΊΠ° NGF β ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΠ-2, ΠΎΠ±Π»Π°Π΄Π°ΡΡΠ΅Π³ΠΎ ΡΠ²ΠΎΠΉΡΡΠ²Π°ΠΌΠΈ Π°Π³ΠΎΠ½ΠΈΡΡΠ° TrkA ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ².
ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π²Π»ΠΈΡΠ½ΠΈΡ ΡΠ°Π±ΠΎΠΌΠΎΡΠΈΠ·ΠΎΠ»Π° Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΡ Π»ΠΎΡΠΈΠ΄Π° Π½Π° ΠΌΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΡΡ ΠΊΠ°ΡΡΠΈΠ½Ρ Π»Π΅Π²ΠΎΠ³ΠΎ ΠΆΠ΅Π»ΡΠ΄ΠΎΡΠΊΠ° ΡΠ΅ΡΠ΄ΡΠ° Ρ ΠΊΡΡΡ Ρ ΠΏΠΎΠ΄ΠΎΡΡΡΡΠΌ ΠΈΠ½ΡΠ°ΡΠΊΡΠΎΠΌ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π°
The purpose of the study. Investigation of the effect of the fabomotizol dihydrochloride systematic therapy on the morphological picture of the heart left ventricle (LV) in rats in the subacute period of myocardial infarction. Materials and methods. Myocardial infarction (MI) modeling was carried out using the A.Selye method. Fabomotizol dihydrochloride was administered to rats intraperitoneally 1 time per day from the 15th to the 28th day after MI at a dose of 15 mg/kg. At the end of the experiment, euthanasia and a pathoanatomic autopsy were performed. Samples of hearts after fixation in formalin and standard wiring were poured into paraffin blocks. Histological sections of the hearts were microscoped in transmitted light. Results. Dilation of the LV cavity and thinning of its walls in animals treated with fabomotizol dihydrochloride are less pronounced than in control rats with MI. In the periinfarction zone of the myocardium in rats treated with fabomotizol dihydrochloride, wave-like deformation and fragmentation of cardiomyocytes is less intense, and the transverse striation of myofibrils, on the contrary, is more pronounced than in the control. In animals treated with fabomotizol dihydrochloride, the periinfarction zone is well vascularized. Conclusion. According to the results of morphological studies performed on a model of subacute MI in rats, it was demonstrated that systematic therapy with fabomotizole dihydrochloride contributes not only to a significant reduction in the necrosis zone, but also to a certain extent prevents the development of early postinfarction remodeling. In rats treated with fabomotizol dihydrochloride, in contrast to control animals, reparative processes prevail in the cardiac muscle. These observations indicate the presence of cardioprotective activity in the drug.Π¦Π΅Π»Ρ. ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π²Π»ΠΈΡΠ½ΠΈΡ ΡΠΈΡΡΠ΅ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΡΠ°Π±ΠΎΠΌΠΎΡΠΈΠ·ΠΎΠ»Π° Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄ΠΎΠΌ Π½Π° ΠΌΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΡΡ ΠΊΠ°ΡΡΠΈΠ½Ρ Π»Π΅Π²ΠΎΠ³ΠΎ ΠΆΠ΅Π»ΡΠ΄ΠΎΡΠΊΠ° (ΠΠ) ΡΠ΅ΡΠ΄ΡΠ° Ρ ΠΊΡΡΡ Π² ΠΏΠΎΠ΄ΠΎΡΡΡΠΎΠΌ ΠΏΠ΅ΡΠΈΠΎΠ΄Π΅ ΠΈΠ½ΡΠ°ΡΠΊΡΠ° ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π° (ΠΠ). ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΠ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ ΠΏΠΎ ΠΌΠ΅ΡΠΎΠ΄Ρ A.Selye. Π€Π°Π±ΠΎΠΌΠΎΡΠΈΠ·ΠΎΠ»Π° Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄ Π²Π²ΠΎΠ΄ΠΈΠ»ΠΈ ΠΊΡΡΡΠ°ΠΌ Π²Π½ΡΡΡΠΈΠ±ΡΡΡΠΈΠ½Π½ΠΎ 1 ΡΠ°Π· Π² ΡΡΡΠΊΠΈ Ρ 15-Π³ΠΎ ΠΏΠΎ 28-ΠΉ Π΄Π΅Π½Ρ ΠΏΠΎΡΠ»Π΅ ΠΠ Π² Π΄ΠΎΠ·Π΅ 15 ΠΌΠ³/ΠΊΠ³. ΠΠΎ ΠΎΠΊΠΎΠ½ΡΠ°Π½ΠΈΠΈ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ° ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ ΡΠ²ΡΠ°Π½Π°Π·ΠΈΡ ΠΈ ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΎΠ°Π½Π°ΡΠΎΠΌΠΈΡΠ΅ΡΠΊΠΎΠ΅ Π²ΡΠΊΡΡΡΠΈΠ΅. ΠΠ±ΡΠ°Π·ΡΡ ΡΠ΅ΡΠ΄Π΅Ρ ΠΏΠΎΡΠ»Π΅ ΡΠΈΠΊΡΠ°ΡΠΈΠΈ Π² ΡΠΎΡΠΌΠ°Π»ΠΈΠ½Π΅ ΠΈ ΡΡΠ°Π½Π΄Π°ΡΡΠ½ΠΎΠΉ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΊΠΈ Π·Π°Π»ΠΈΠ²Π°Π»ΠΈ Π² ΠΏΠ°ΡΠ°ΡΠΈΠ½ΠΎΠ²ΡΠ΅ Π±Π»ΠΎΠΊΠΈ. ΠΠΈΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΡΠ΅Π·Ρ ΡΠ΅ΡΠ΄Π΅Ρ ΠΌΠΈΠΊΡΠΎΡΠΊΠΎΠΏΠΈΡΠΎΠ²Π°Π»ΠΈ Π² ΠΏΡΠΎΡ
ΠΎΠ΄ΡΡΠ΅ΠΌ ΡΠ²Π΅ΡΠ΅. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΠΈΠ»Π°ΡΠ°ΡΠΈΡ ΠΏΠΎΠ»ΠΎΡΡΠΈ ΠΠ ΠΈ ΠΈΡΡΠΎΠ½ΡΠ΅Π½ΠΈΠ΅ Π΅Π³ΠΎ ΡΡΠ΅Π½ΠΎΠΊ Ρ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ
, ΠΏΠΎΠ»ΡΡΠ°Π²ΡΠΈΡ
ΡΠ°Π±ΠΎΠΌΠΎΡΠΈΠ·ΠΎΠ»Π° Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄, ΠΌΠ΅Π½Π΅Π΅ Π²ΡΡΠ°ΠΆΠ΅Π½Ρ, ΡΠ΅ΠΌ Ρ ΠΊΠΎΠ½ΡΡΠΎΠ»ΡΠ½ΡΡ
ΠΊΡΡΡ Ρ ΠΠ. Π ΠΏΠ΅ΡΠΈΠΈΠ½ΡΠ°ΡΠΊΡΠ½ΠΎΠΉ Π·ΠΎΠ½Π΅ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π° Ρ ΠΊΡΡΡ, ΠΏΠΎΠ»ΡΡΠ°Π²ΡΠΈΡ
ΡΠ°Π±ΠΎΠΌΠΎΡΠΈΠ·ΠΎΠ»Π° Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄, Π²ΠΎΠ»Π½ΠΎΠΎΠ±ΡΠ°Π·Π½Π°Ρ Π΄Π΅ΡΠΎΡΠΌΠ°ΡΠΈΡ ΠΈ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠ°ΡΠΈΡ ΠΊΠ°ΡΠ΄ΠΈΠΎΠΌΠΈΠΎΡΠΈΡΠΎΠ² (ΠΠ) ΠΌΠ΅Π½Π΅Π΅ ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½Π°, Π° ΠΏΠΎΠΏΠ΅ΡΠ΅ΡΠ½Π°Ρ ΠΈΡΡΠ΅ΡΡΠ΅Π½Π½ΠΎΡΡΡ ΠΌΠΈΠΎΡΠΈΠ±ΡΠΈΠ»Π», Π½Π°ΠΏΡΠΎΡΠΈΠ², Π±ΠΎΠ»Π΅Π΅ Π²ΡΡΠ°ΠΆΠ΅Π½Π°, ΡΠ΅ΠΌ Π² ΠΊΠΎΠ½ΡΡΠΎΠ»Π΅. Π£ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ
, ΠΏΠΎΠ»ΡΡΠ°Π²ΡΠΈΡ
ΡΠ°Π±ΠΎΠΌΠΎΡΠΈΠ·ΠΎΠ»Π° Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄, ΠΏΠ΅ΡΠΈΠΈΠ½ΡΠ°ΡΠΊΡΠ½Π°Ρ Π·ΠΎΠ½Π° Ρ
ΠΎΡΠΎΡΠΎ Π²Π°ΡΠΊΡΠ»ΡΡΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π°. ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. Π‘ΠΎΠ³Π»Π°ΡΠ½ΠΎ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ°ΠΌ ΠΌΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΡΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ, Π²ΡΠΏΠΎΠ»Π½Π΅Π½Π½ΡΡ
Π½Π° ΠΌΠΎΠ΄Π΅Π»ΠΈ ΠΏΠΎΠ΄ΠΎΡΡΡΠΎΠΉ ΠΈΡΠ΅ΠΌΠΈΠΈ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π° Ρ ΠΊΡΡΡ, ΠΏΡΠΎΠ΄Π΅ΠΌΠΎΠ½ΡΡΡΠΈΡΠΎΠ²Π°Π½ΠΎ, ΡΡΠΎ ΡΠΈΡΡΠ΅ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠ°Ρ ΡΠ΅ΡΠ°ΠΏΠΈΡ ΡΠ°Π±ΠΎΠΌΠΎΡΠΈΠ·ΠΎΠ»Π° Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄ΠΎΠΌ ΡΠΏΠΎΡΠΎΠ±ΡΡΠ²ΡΠ΅Ρ Π½Π΅ ΡΠΎΠ»ΡΠΊΠΎ Π·Π½Π°ΡΠΈΠΌΠΎΠΌΡ ΡΠΌΠ΅Π½ΡΡΠ΅Π½ΠΈΡ Π·ΠΎΠ½Ρ Π½Π΅ΠΊΡΠΎΠ·Π°, Π½ΠΎ ΠΈ Π² ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ½Π½ΠΎΠΉ ΠΌΠ΅ΡΠ΅ ΠΏΡΠ΅ΠΏΡΡΡΡΠ²ΡΠ΅Ρ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΠ°Π½Π½Π΅Π³ΠΎ ΠΏΠΎΡΡΠΈΠ½ΡΠ°ΡΠΊΡΠ½ΠΎΠ³ΠΎ ΡΠ΅ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ. Π£ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ
, ΠΏΠΎΠ»ΡΡΠ°Π²ΡΠΈΡ
ΡΠ°Π±ΠΎΠΌΠΎΡΠΈΠ·ΠΎΠ»Π° Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄, Π² ΠΎΡΠ»ΠΈΡΠΈΠ΅ ΠΎΡ ΠΊΠΎΠ½ΡΡΠΎΠ»ΡΠ½ΡΡ
ΠΊΡΡΡ, Π² ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎΠΉ ΠΌΡΡΡΠ΅ ΠΏΡΠ΅ΠΎΠ±Π»Π°Π΄Π°ΡΡ ΡΠ΅ΠΏΠ°ΡΠ°ΡΠΈΠ²Π½ΡΠ΅ ΠΏΡΠΎΡΠ΅ΡΡΡ. ΠΡΠΈ Π½Π°Π±Π»ΡΠ΄Π΅Π½ΠΈΡ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡΡ ΠΎ Π½Π°Π»ΠΈΡΠΈΠΈ Ρ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ° ΠΊΠ°ΡΠ΄ΠΈΠΎΠΏΡΠΎΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ
ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π²Π»ΠΈΡΠ½ΠΈΡ ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΡ ΠΌΠ΅ΡΠΎΠΊΡΠΈ-Π³ΡΡΠΏΠΏΡ Π½Π° ΠΊΠ°ΡΠ΄ΠΈΠΎΡΡΠΎΠΏΠ½ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΠΠ-802
A new compound ALM-803 (trihydrochloride N1-(3,4,5-trimethoxybenzyl)-N2-{2-[(3,4,5-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine) was synthesized as analog of ALM 802, differing from it by the position of the methoxy groups in the phenyl rings. It is established that this structural change leads to the disappearance of anti-ischemic activity and antiarrhythmic activity on the model of aconitine arrhythmia in rats, but the antiarrhythmic activity on models of chloride-calcium arrhythmia and electrical fibrillation of the heart of rats remained (1 mg/kg, intravenously).Π‘ΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½ΠΎ Π½ΠΎΠ²ΠΎΠ΅ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅ ΠΠΠ-803 (ΡΡΠΈΠ³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄ β-(3,4,5-ΡΡΠΈΠΌΠ΅ΡΠΎΠΊΡΠΈΠ±Π΅Π½Π·ΠΈΠ»)-β-{2-[(3,4,5-ΡΡΠΈΠΌΠ΅ΡΠΎΠΊΡΠΈΠ±Π΅Π½Π·ΠΈΠ») Π°ΠΌΠΈΠ½ΠΎ]-ΡΡΠΈΠ»}-1,2-ΡΡΠ°Π½Π΄ΠΈΠ°ΠΌΠΈΠ½Π°) - Π°Π½Π°Π»ΠΎΠ³ ΠΠΠ-802, ΠΎΡΠ»ΠΈΡΠ°ΡΡΠΈΠΉΡΡ ΠΎΡ Π½Π΅Π³ΠΎ ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΠ΅ΠΌ ΠΌΠ΅ΡΠΎΠΊΡΠΈ-Π³ΡΡΠΏΠΏ Π² ΡΠ΅Π½ΠΈΠ»ΡΠ½ΡΡ
ΠΊΠΎΠ»ΡΡΠ°Ρ
. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ ΡΡΠΎ ΡΡΡΡΠΊΡΡΡΠ½ΠΎΠ΅ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΠΈΡΡΠ΅Π·Π½ΠΎΠ²Π΅Π½ΠΈΡ Π°Π½ΡΠΈΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈ Π°Π½ΡΠΈΠ°ΡΠΈΡΠΌΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π½Π° ΠΌΠΎΠ΄Π΅Π»ΠΈ Π°ΠΊΠΎΠ½ΠΈΡΠΈΠ½ΠΎΠ²ΠΎΠΉ Π°ΡΠΈΡΠΌΠΈΠΈ Ρ ΠΊΡΡΡ, Π½ΠΎ ΠΏΡΠΈ ΡΡΠΎΠΌ Π°Π½ΡΠΈΠ°ΡΠΈΡΠΌΠΈΡΠ΅ΡΠΊΠ°Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π½Π° ΠΌΠΎΠ΄Π΅Π»ΡΡ
Ρ
Π»ΠΎΡΠΈΠ΄ΠΊΠ°Π»ΡΡΠΈΠ΅Π²ΠΎΠΉ Π°ΡΠΈΡΠΌΠΈΠΈ ΠΈ ΡΠ»Π΅ΠΊΡΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΈΠ±ΡΠΈΠ»Π»ΡΡΠΈΠΈ ΠΆΠ΅Π»ΡΠ΄ΠΎΡΠΊΠΎΠ² ΡΠ΅ΡΠ΄ΡΠ° ΠΊΡΡΡ ΡΠΎΡ
ΡΠ°Π½ΡΠ΅ΡΡΡ (1 ΠΌΠ³/ΠΊΠ³, Π²Π½ΡΡΡΠΈΠ²Π΅Π½Π½ΠΎ)
ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΊΠ°ΡΠ΄ΠΈΠΎΡΡΠΎΠΏΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΎΡΡΠΎ-Π°Π»ΠΊΠΎΠΊΡΠΈ Π°Π½Π°Π»ΠΎΠ³ΠΎΠ² ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΠΠ-802
New ortho-alkoxy analogs of the compound ALM-802 1a (N1-(2-methoxybenzyl)-N2-[2-((2-methoxybenzyl)amino)ethyl]ethane-1,2-diamine trihydrochloride) and 1b (N1-(2-ethoxybenzyl)-N2-[2-((2-ethoxybenzyl)amino)ethyl]ethane-1,2-diamine trihydrochloride), which differ from it by the presence of alkoxy groups in the phenyl rings only in the ortho positions. It was established that these structural changes lead to the disappearance of anti-ischemic activity. At the same time, antiarrhythmic activity was revealed in compound 1b on the models of aconitine and calcium chloride arrhythmias in rats (1 mg / kg, intravenously), which was absent in 1a.Π‘ΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Ρ Π½ΠΎΠ²ΡΠ΅ ΠΎΡΡΠΎ-Π°Π»ΠΊΠΎΠΊΡΠΈ Π°Π½Π°Π»ΠΎΠ³ΠΈ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΠΠ-802 β 1a (N1-(2-ΠΌΠ΅ΡΠΎΠΊΡΠΈΠ±Π΅Π½Π·ΠΈΠ»)-N2-[2-((2-ΠΌΠ΅ΡΠΎΠΊΡΠΈΠ±Π΅Π½Π·ΠΈΠ»)Π°ΠΌΠΈΠ½ΠΎ)ΡΡΠΈΠ»] ΡΡΠ°Π½-1,2-Π΄ΠΈΠ°ΠΌΠΈΠ½ ΡΡΠΈΠ³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄) ΠΈ 1b (N1-(2-ΡΡΠΎΠΊΡΠΈΠ±Π΅Π½Π·ΠΈΠ»)-N2-[2-((2-ΡΡΠΎΠΊΡΠΈΠ±Π΅Π½Π·ΠΈΠ»)Π°ΠΌΠΈΠ½ΠΎ)ΡΡΠΈΠ»]ΡΡΠ°Π½-1,2-Π΄ΠΈΠ°ΠΌΠΈΠ½ ΡΡΠΈΠ³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄), ΠΎΡΠ»ΠΈΡΠ°ΡΡΠΈΠ΅ΡΡ ΠΎΡ Π½Π΅Π³ΠΎ Π½Π°Π»ΠΈΡΠΈΠ΅ΠΌ Π°Π»ΠΊΠΎΠΊΡΠΈ-Π³ΡΡΠΏΠΏ Π² ΡΠ΅Π½ΠΈΠ»ΡΠ½ΡΡ
ΠΊΠΎΠ»ΡΡΠ°Ρ
ΡΠΎΠ»ΡΠΊΠΎ Π² ΠΎΡΡΠΎ-ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΡΡ
. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ ΡΡΠΈ ΡΡΡΡΠΊΡΡΡΠ½ΡΠ΅ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡ ΠΊ ΠΈΡΡΠ΅Π·Π½ΠΎΠ²Π΅Π½ΠΈΡ Π°Π½ΡΠΈΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ. Π ΡΠΎ ΠΆΠ΅ Π²ΡΠ΅ΠΌΡ Ρ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ 1b Π²ΡΡΠ²Π»Π΅Π½Π° Π°Π½ΡΠΈΠ°ΡΠΈΡΠΌΠΈΡΠ΅ΡΠΊΠ°Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π½Π° ΠΌΠΎΠ΄Π΅Π»ΡΡ
Π°ΠΊΠΎΠ½ΠΈΡΠΈΠ½ΠΎΠ²ΠΎΠΉ ΠΈ Ρ
Π»ΠΎΡΠΈΠ΄ΠΊΠ°Π»ΡΡΠΈΠ΅Π²ΠΎΠΉ Π°ΡΠΈΡΠΌΠΈΠΈ Ρ ΠΊΡΡΡ (1 ΠΌΠ³/ΠΊΠ³, Π²Π½ΡΡΡΠΈΠ²Π΅Π½Π½ΠΎ), ΠΊΠΎΡΠΎΡΠ°Ρ ΠΎΡΡΡΡΡΡΠ²ΠΎΠ²Π°Π»Π° Ρ 1a
Antioxidants in the Treatment of Chronic Diffuse Liver Diseases (the Results of the βMAXARβ Observational Program)
In the Russian Federation, liver diseases are most frequently represented by two their nosological forms, i.e., nonalcoholic and alcoholic fatty liver disease (NAFLD and ALD). A successful management of such patients, along with improving the functional state of the liver, requires a careful analysis of patientsβ nonspecific complaints. In particular, it is important to investigate asthenic syndrome, which can indirectly result in the exacerbation of liver diseases, thus incurring additional economic costs to national healthcare systems. Therefore, the elucidation of the nature of asthenic syndrome and a search for methods for its resolution seem to be highly relevant research tasks.Aim. This study aims to investigate the effect of the antioxidant drug (the extract of the Amur maackia wood) on the organic and functional components of asthenic syndrome in patients with NAFLD and ALD, who do not show signs of the disease decompensation. Materials and methods. An observational program was carried out under the conditions of daily clinical practice in three Russian cities: Moscow, Chelyabinsk and Vladivostok. 80 patients (40 with NAFLD, 40 with ALD) were comprehensively examined according to a developed program. A number of laboratory indicators that reveal inflammatory processes in the liver were studied, including leukocytes, ESR, ALT, AST, GGTP and CRP. The patientsβ psycho-emotional status was assessed using a Daily Fatigue Impact Scale (D-FIS) and a four-dimensional scale for assessing distress, depression, anxiety and somatisation (4DSQ). Results. According to the D-FIS questionnaire, all the patients showed fatigue. According to the 4DSQ questionnaire, a correlation of distress with the level of laboratory indicators was revealed among all the patients. No such a correlation was noted for depression and anxiety in the patients with NAFLD. On the contrary, in the case of ALD, all psycho-emotional disorders (except for somatisation) were positively correlated with the markers of inflammation. It is shown that asthenic syndrome in patients with both NAFLD and ALD has a complex origin, being associated both with inflammatory processes in the liver and psycho-emotional disorders. In all cases under study, the prescription of the preparation led to a decrease in the studied laboratory indicators (inflammation markers) and an increase in the patientsβ psycho-emotional status. The latter improvement was manifested in the reduction of distress, depression, anxiety and somatisation, according to the 4DSQ questionnaire, as well as in the reduction of fatigue, according to the D-FIS questionnaire.Conclusion. The results of the observational program have shown that patients with NAFLD and ALD frequently experience such components of asthenic syndrome as distress, depression, anxiety, somatisation and fatigue. The prescription of the preparation is found to result in a decrease in laboratory inflammatory indicators. In addition, the preparation is determined to positively affect the components of asthenic syndrome in patients with NAFLD and ALD. In the course of the treatment, no clinically significant side effects were documented
Antioxidants in the Treatment of Chronic Diffuse Liver Diseases (the Results of the βMAXARβ Observational Program)
In the Russian Federation, liver diseases are most frequently represented by two their nosological forms, i.e., nonalcoholic and alcoholic fatty liver disease (NAFLD and ALD). A successful management of such patients, along with improving the functional state of the liver, requires a careful analysis of patientsβ nonspecific complaints. In particular, it is important to investigate asthenic syndrome, which can indirectly result in the exacerbation of liver diseases, thus incurring additional economic costs to national healthcare systems. Therefore, the elucidation of the nature of asthenic syndrome and a search for methods for its resolution seem to be highly relevant research tasks.Aim. This study aims to investigate the effect of the antioxidant drug (the extract of the Amur maackia wood) on the organic and functional components of asthenic syndrome in patients with NAFLD and ALD, who do not show signs of the disease decompensation. Materials and methods. An observational program was carried out under the conditions of daily clinical practice in three Russian cities: Moscow, Chelyabinsk and Vladivostok. 80 patients (40 with NAFLD, 40 with ALD) were comprehensively examined according to a developed program. A number of laboratory indicators that reveal inflammatory processes in the liver were studied, including leukocytes, ESR, ALT, AST, GGTP and CRP. The patientsβ psycho-emotional status was assessed using a Daily Fatigue Impact Scale (D-FIS) and a four-dimensional scale for assessing distress, depression, anxiety and somatisation (4DSQ). Results. According to the D-FIS questionnaire, all the patients showed fatigue. According to the 4DSQ questionnaire, a correlation of distress with the level of laboratory indicators was revealed among all the patients. No such a correlation was noted for depression and anxiety in the patients with NAFLD. On the contrary, in the case of ALD, all psycho-emotional disorders (except for somatisation) were positively correlated with the markers of inflammation. It is shown that asthenic syndrome in patients with both NAFLD and ALD has a complex origin, being associated both with inflammatory processes in the liver and psycho-emotional disorders. In all cases under study, the prescription of the preparation led to a decrease in the studied laboratory indicators (inflammation markers) and an increase in the patientsβ psycho-emotional status. The latter improvement was manifested in the reduction of distress, depression, anxiety and somatisation, according to the 4DSQ questionnaire, as well as in the reduction of fatigue, according to the D-FIS questionnaire.Conclusion. The results of the observational program have shown that patients with NAFLD and ALD frequently experience such components of asthenic syndrome as distress, depression, anxiety, somatisation and fatigue. The prescription of the preparation is found to result in a decrease in laboratory inflammatory indicators. In addition, the preparation is determined to positively affect the components of asthenic syndrome in patients with NAFLD and ALD. In the course of the treatment, no clinically significant side effects were documented