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Π‘ΠΈΠ½ΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°Π½Π°Π»ΠΎΠ³ Π»Π΅ΠΉ-ΡΠ½ΠΊΠ΅ΡΠ°Π»ΠΈΠ½Π° ΠΏΡΠ΅Π΄ΠΎΡΠ²ΡΠ°ΡΠ°Π΅Ρ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ Π½Π΅ΠΉΡΡΠΎΡΠΈΠ»ΠΎΠ² ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ Π±Π°ΠΊΡΠ΅ΡΠΈΠ°Π»ΡΠ½ΡΡ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠΎΠ²
Background: Neutrophil activation is aΒ mandatory stage and aΒ sensitive marker of systemic inflammatory response. The development of this condition is associated with subsequent multiple organ failure which is the main indication for the patients stay in the intensive care unit. The search for drugs that could prevent the development of systemic inflammatory response and reduce mortality remains an urgent task of anesthesiology/resuscitation.Aim: To study the anti-inflammatory effect of dalargin, aΒ synthetic analogue of lei-enkephalin, on human neutrophils in vitro.Materials and methods: The study was performed on blood neutrophils isolated from 5 healthy donors. AΒ proportion of neutrophils were activated by 10 mkM formil-Met-Leu-Pro (fMLP) and 100 ng/mL lipopolysaccharide (LPS) with subsequent assessment of their activity by fluorescent antibodies to the degranulation markers CD11b and CD66b. Thereafter intact and activated neutrophils were treated with dalargin solution at concentrations of 50 and 100Β mcg/mL.Results: Dalargin at 100Β mcg/mL reduced the expression of CD11b molecules on the surface of intact neutrophils by 5.5-fold (p=0.008). On the contrary, LPS at aΒ dose of 100Β ng/mL increased the expression of the same molecules by 46% (p=0.08). The addition of dalargin at 50Β mcg/mL to LPS-activated neutrophils reduced the expression of CD11b molecules (p=0.016). The addition of dalargin at 50Β mcg/mL to fMLP-activated neutrophils significantly (p=0.008) reduced the expression of CD11b molecules and reversed their expression virtually to the level of the control. The addition of dalargin at 100Β mcg/mL to neutrophils activated by fMLP at 10Β mkM reduced the expression of CD11b on their surface to aΒ level below the control by 23% (p=0.08).Conclusion: Dalargin at the studied concentrations has an anti-inflammatory effect on both intact and pre-activated bacterial components of neutrophils, thus inhibiting the process of activation and degranulation in aΒ dose-dependent manner.Β ΠΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ. ΠΠΊΡΠΈΠ²Π°ΡΠΈΡ Π½Π΅ΠΉΡΡΠΎΡΠΈΠ»ΠΎΠ²Β β ΠΎΠ±ΡΠ·Π°ΡΠ΅Π»ΡΠ½ΡΠΉ ΡΡΠ°ΠΏ ΠΈΒ ΡΡΠ²ΡΡΠ²ΠΈΡΠ΅Π»ΡΠ½ΡΠΉ ΠΌΠ°ΡΠΊΠ΅Ρ ΡΠΈΡΡΠ΅ΠΌΠ½ΠΎΠ³ΠΎ Π²ΠΎΡΠΏΠ°Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ ΠΎΡΠ²Π΅ΡΠ°. Π‘Β ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ΠΌ ΡΡΠΎΠ³ΠΎ ΡΠΎΡΡΠΎΡΠ½ΠΈΡ ΡΠΎΠΏΡΡΠΆΠ΅Π½ΠΎ Π²ΠΎΠ·Π½ΠΈΠΊΠ½ΠΎΠ²Π΅Π½ΠΈΠ΅ ΠΏΠΎΠ»ΠΈΠΎΡΠ³Π°Π½Π½ΠΎΠΉ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΡΡΠΈΒ β ΠΎΡΠ½ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΈΡ Π΄Π»Ρ ΠΏΡΠ΅Π±ΡΠ²Π°Π½ΠΈΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Π²Β ΠΎΡΠ΄Π΅Π»Π΅Π½ΠΈΠΈ ΡΠ΅Π°Π½ΠΈΠΌΠ°ΡΠΈΠΈ. ΠΠΎΠΈΡΠΊ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ², ΡΠΏΠΎΡΠΎΠ±Π½ΡΡ
ΠΏΡΠ΅Π΄ΠΎΡΠ²ΡΠ°ΡΠΈΡΡ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ ΡΠΈΡΡΠ΅ΠΌΠ½ΠΎΠ³ΠΎ Π²ΠΎΡΠΏΠ°Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ ΠΎΡΠ²Π΅ΡΠ° ΠΈΒ ΡΠ½ΠΈΠ·ΠΈΡΡ Π»Π΅ΡΠ°Π»ΡΠ½ΠΎΡΡΡ, ΠΎΡΡΠ°Π΅ΡΡΡ Π°ΠΊΡΡΠ°Π»ΡΠ½ΠΎΠΉ Π·Π°Π΄Π°ΡΠ΅ΠΉ Π°Π½Π΅ΡΡΠ΅Π·ΠΈΠΎΠ»ΠΎΠ³ΠΈΠΈΡΠ΅Π°Π½ΠΈΠΌΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΠΈ.Π¦Π΅Π»ΡΒ β ΠΈΠ·ΡΡΠΈΡΡ ΠΏΡΠΎΡΠΈΠ²ΠΎΠ²ΠΎΡΠΏΠ°Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΡΠΈΠ½ΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΎΠ³Π° Π»Π΅ΠΉ-ΡΠ½ΠΊΠ΅ΡΠ°Π»ΠΈΠ½Π° (ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ Π΄Π°Π»Π°ΡΠ³ΠΈΠ½) Π½Π° Π½Π΅ΠΉΡΡΠΎΡΠΈΠ»Π°Ρ
ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° in vitro.ΠΠ°ΡΠ΅ΡΠΈΠ°Π» ΠΈΒ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΎΡΡ Π½Π° Π²ΡΠ΄Π΅Π»Π΅Π½Π½ΡΡ
ΠΈΠ· ΠΊΡΠΎΠ²ΠΈ 5Β Π·Π΄ΠΎΡΠΎΠ²ΡΡ
Π΄ΠΎΠ½ΠΎΡΠΎΠ² Π½Π΅ΠΉΡΡΠΎΡΠΈΠ»Π°Ρ
, ΡΠ°ΡΡΡ ΠΈΠ· ΠΊΠΎΡΠΎΡΡΡ
Π°ΠΊΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π»ΠΈ ΡΒ ΠΏΠΎΠΌΠΎΡΡΡ 10Β ΠΌΠΊM ΡΠΎΡΠΌΠΈΠ»-ΠΠ΅Ρ-ΠΠ΅ΠΉ-ΠΡΠΎ (fMLP) ΠΈΒ 100Β Π½Π³/ΠΌΠ» Π»ΠΈΠΏΠΎΠΏΠΎΠ»ΠΈΡΠ°Ρ
Π°ΡΠΈΠ΄Π° (ΠΠΠ‘) ΠΈΒ Π·Π°ΡΠ΅ΠΌ ΠΎΡΠ΅Π½ΠΈΠ²Π°Π»ΠΈ ΠΈΡ
Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΡΒ ΠΏΠΎΠΌΠΎΡΡΡ ΡΠ»ΡΠΎΡΠ΅ΡΡΠ΅Π½ΡΠ½ΡΡ
Π°Π½ΡΠΈΡΠ΅Π» ΠΊΒ ΠΌΠ°ΡΠΊΠ΅ΡΠ°ΠΌ Π΄Π΅Π³ΡΠ°Π½ΡΠ»ΡΡΠΈΠΈ CD11b ΠΈΒ CD66b. ΠΠ½ΡΠ°ΠΊΡΠ½ΡΠ΅ ΠΈΒ Π°ΠΊΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ Π½Π΅ΠΉΡΡΠΎΡΠΈΠ»Ρ ΠΎΠ±ΡΠ°Π±Π°ΡΡΠ²Π°Π»ΠΈ ΡΠ°ΡΡΠ²ΠΎΡΠΎΠΌ Π΄Π°Π»Π°ΡΠ³ΠΈΠ½Π° Π²Β ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡΡ
50Β ΠΈΒ 100Β ΠΌΠΊΠ³/ΠΌΠ».Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΠ°Π»Π°ΡΠ³ΠΈΠ½ Π²Β ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ 100Β ΠΌΠΊΠ³/ΠΌΠ» Π²Β 5,5Β ΡΠ°Π·Π° (Ρ=0,008) ΡΠ½ΠΈΠΆΠ°Π΅Ρ ΡΡΠΎΠ²Π΅Π½Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΠΌΠΎΠ»Π΅ΠΊΡΠ» CD11b Π½Π° ΠΏΠΎΠ²Π΅ΡΡ
Π½ΠΎΡΡΠΈ ΠΈΠ½ΡΠ°ΠΊΡΠ½ΡΡ
Π½Π΅ΠΉΡΡΠΎΡΠΈΠ»ΠΎΠ², Π°Β ΠΠΠ‘ Π²Β Π΄ΠΎΠ·Π΅ 100Β Π½Π³/ΠΌΠ», Π½Π°ΠΏΡΠΎΡΠΈΠ², ΡΠ²Π΅Π»ΠΈΡΠΈΠ²Π°Π΅Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΡΠ΅Ρ
ΠΆΠ΅ ΠΌΠΎΠ»Π΅ΠΊΡΠ» Π½Π° 46% (Ρ=0,08). ΠΠΎΠ±Π°Π²Π»Π΅Π½ΠΈΠ΅ Π΄Π°Π»Π°ΡΠ³ΠΈΠ½Π° Π²Β ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ 50Β ΠΌΠΊΠ³/ΠΌΠ» ΠΊΒ Π½Π΅ΠΉΡΡΠΎΡΠΈΠ»Π°ΠΌ, Π°ΠΊΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½Π½ΡΠΌ ΠΠΠ‘, ΡΠΌΠ΅Π½ΡΡΠ°Π΅Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΠΌΠΎΠ»Π΅ΠΊΡΠ» CD11b (Ρ=0,016). ΠΠΎΠ±Π°Π²Π»Π΅Π½ΠΈΠ΅ Π΄Π°Π»Π°ΡΠ³ΠΈΠ½Π° Π²Β ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡΡ
50Β ΠΌΠΊΠ³/ΠΌΠ» ΠΊΒ Π°ΠΊΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½Π½ΡΠΌ fMLP Π½Π΅ΠΉΡΡΠΎΡΠΈΠ»Π°ΠΌ Π·Π½Π°ΡΠΈΠΌΠΎ (Ρ=0,008) ΡΠΌΠ΅Π½ΡΡΠ°Π΅Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΠΌΠΎΠ»Π΅ΠΊΡΠ» CD11b ΠΈΒ Π²ΠΎΠ·Π²ΡΠ°ΡΠ°Π΅Ρ Π΅Π΅ ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΈ ΠΊΒ ΡΡΠΎΠ²Π½Ρ ΠΊΠΎΠ½ΡΡΠΎΠ»Ρ. ΠΠ°Π»Π°ΡΠ³ΠΈΠ½Π°, Π΄ΠΎΠ±Π°Π²Π»Π΅Π½Π½ΡΠΉ Π²Β ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ 100Β ΠΌΠΊΠ³/ΠΌΠ» ΠΊΒ Π½Π΅ΠΉΡΡΠΎΡΠΈΠ»Π°ΠΌ, Π°ΠΊΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½Π½ΡΠΌ fMLP Π²Β Π΄ΠΎΠ·Π΅ 10Β ΠΌΠΊΠ, ΡΠΌΠ΅Π½ΡΡΠ°Π΅Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ CD11b Π½Π° ΠΈΡ
ΠΏΠΎΠ²Π΅ΡΡ
Π½ΠΎΡΡΠΈ Π΄ΠΎ ΡΡΠΎΠ²Π½Ρ Π½ΠΈΠΆΠ΅ ΠΊΠΎΠ½ΡΡΠΎΠ»Ρ Π½Π° 23% (Ρ=0,08).ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠ°Π»Π°ΡΠ³ΠΈΠ½ Π²Β ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½Π½ΡΡ
ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡΡ
ΠΎΠΊΠ°Π·ΡΠ²Π°Π΅Ρ ΠΏΡΠΎΡΠΈΠ²ΠΎΠ²ΠΎΡΠΏΠ°Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΠΊΠ°ΠΊ Π½Π° ΠΈΠ½ΡΠ°ΠΊΡΠ½ΡΠ΅, ΡΠ°ΠΊ ΠΈΒ Π½Π° ΠΏΡΠ΅Π΄Π°ΠΊΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ Π±Π°ΠΊΡΠ΅ΡΠΈΠ°Π»ΡΠ½ΡΠΌΠΈ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠ°ΠΌΠΈ Π½Π΅ΠΉΡΡΠΎΡΠΈΠ»Ρ, ΠΈΠ½Π³ΠΈΠ±ΠΈΡΡΡ ΠΏΡΠΎΡΠ΅ΡΡ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠΈ ΠΈΒ Π΄Π΅Π³ΡΠ°Π½ΡΠ»ΡΡΠΈΠΈ Π΄ΠΎΠ·ΠΎΠ·Π°Π²ΠΈΡΠΈΠΌΡΠΌ ΠΎΠ±ΡΠ°Π·ΠΎΠΌ.