Wpływ leczenia za pomocą [Pyr1]apeliny-13 na zmniejszenie remodelingu i apoptozy w sercach szczurów

Background: Ischaemic heart disease is the main cause of mortality in the world. After myocardial infarction (MI) cardiomyocytes apoptosis and ventricular remodelling have occurred. Apelin is a peptide that has been shown to exert cardioprotective effects. Aim: The aim of this study was to investigate the anti-apoptotic and anti-remodelling effects of [Pyr1]apelin-13 in the rat model of post-MI. Methods: Thirty-six male Wistar rats were randomly divided into three groups: (1) sham, (2) MI, and (3) MI treated with [Pyr1] apelin-13 (MI+Apel). MI animals were subjected to 30-min ligation of the left anterior descending coronary artery (LAD) and 14 days of reperfusion. Twenty-four hours after LAD ligation, [Pyr1]apelin-13 (10 nmol/kg/day, i.p.) was administered for five consecutive days. Hypertrophic parameters, left ventricular (LV) remodelling, and gene expression of Apel, apelin receptor (Apelr), Bax, caspase-3 (Casp-3), and Bcl-2 by real-time polymerase chain reaction and cardiomyocytes apoptosis by TUNEL immunostaining were assessed on day 14 post-MI. Results: Post-infarct treatment with [Pyr1]apelin-13 improved myocardial hypertrophic and LV remodelling parameters and led to a significant increase in the expression of Apel, Apelr, and Bcl-2, and a decrease in the expression of Bax and Casp-3. Furthermore, treatment with [Pyr1]apelin-13 decreased cardiomyocyte apoptosis. Conclusions: [Pyr1]apelin-13 has anti-hypertrophic, anti-remodelling, and anti-apoptotic effects via overexpression of Apel, Apelr, and Bcl-2 and reduces gene expression of Bax and Casp-3 in the infarcted myocardium, which can in turn lead to repair myocardium.  Wstęp: Choroba niedokrwienna serca jest główną przyczyną zgonów na świecie. Po zawale serca (MI) obserwuje się apoptozę kardiomiocytów i remodeling komór. Wykazano, że białkowa substancja, apelina, ma działanie kardioprotekcyjne. Cel: Badanie przeprowadzono w celu oceny ochronnego działania [Pyr1]apeliny-13 w postaci zmniejszenia apoptozy i remodelingu w szczurzym modelu MI. Metody: Trzydzieści sześć szczurów Wistar płci męskiej podzielono losowo na trzy grupy: (1) grupa kontrolna, (2) grupa z MI oraz (3) grupa z MI poddana leczeniu za pomocą [Pyr1]apeliny-13 (MI+Apel). U części zwierząt podwiązano na 30 min tętnicę przednią zstępującą lewą (LAD), po czym nastąpił 14-dniowy okres reperfuzji. [Pyr1]apelinę-13 (10 nmol/kg/d., i.p.) podawano przez 5 kolejnych dni, przy czym pierwszą dawkę podano 24 h po podwiązaniu LAD. Po 14 dniach od MI oceniono wskaźniki przerostu mięśnia sercowego i remodeling lewej komory (LV), a także ekspresję genów Apel, receptora apeliny (Apelr), Bax, caspase-3 (Casp-3) oraz Bcl-2 metodą polimerazowej reakcji łańcuchowej (PCR) w czasie rzeczywistym i apoptozę kardiomiocytów metodą immunobarwienia TUNEL. Wyniki: Leczenie za pomocą [Pyr1]apeliny-13 u zwierząt po MI spowodowało poprawę parametrów przerostu mięśnia sercowego i przebudowy LV, a także istotne zwiększenie ekspresji genów Apel, Apelr i Bcl-2 oraz zmniejszenie ekspresji genów Bax i Casp-3. Ponadto stosowanie [Pyr1]apeliny-13 wpłynęło na zmniejszenie apoptozy kardiomiocytów. Wnioski: [Pyr1]apelina-13 zmniejsza przerost mięśnia sercowego i remodeling oraz ma działanie przeciwapoptotyczne poprzez zwiększenie ekspresji genów Apel, Apelr i Bcl-2 oraz zmniejszenie ekspresji genów Bax i Casp-3 w objętym zawałem miokardium, co może prowadzić do naprawy uszkodzonego mięśnia sercowego

Naringenin improves learning and memory in an Alzheimer's disease rat model : Insights into the underlying mechanisms

Alzheimer's disease (AD) is one of the prevalent neurological disorders of the central nervous system hallmarked by increased beta-amyloid (Aβ) deposition and ensuing learning and memory deficit. In the present study, the beneficial effect of naringenin on improvement of learning and memory was evaluated in an Alzheimer's disease rat model. The Aβ-injected rats showed a lower alternation score in Y-maze task, impairment of retention and recall capability in passive avoidance test, and lower correct choices and higher errors in radial arm maze (RAM) task as compared to sham group in addition to enhanced oxidative stress and apoptosis. Naringenin, but not a combination of naringenin and fulvestrant (an estrogenic receptor antagonist) significantly improved the performance of Aβ-injected rats in passive avoidance and RAM tasks. Naringenin pretreatment of Aβ-injected rats also lowered hippocampal malondialdehyde (MDA) with no significant effect on nitrite and superoxide dismutase (SOD) activity in addition to lowering apoptosis. These results suggest naringenin pretreatment attenuates Aβ-induced impairment of learning and memory through mitigation of lipid peroxidation and apoptosis and its beneficial effect is somewhat mediated via estrogenic pathway.Funding agencies: Cellular and Molecular Research Center at Iran University of Medical Sciences (Tehran) [2011.37]; Linkoping University (Linkoping, Sweden)</p

Effect of bone marrow derived mesenchymal stem cells on lung pathology and inflammation in ovalbumin-induced asthma in mouse

Objective(s):Bone marrow-derived mesenchymal stem cells (BMSCs) have attracted significant interest to treat asthma and its complication. In this study, the effects of BMSCs on lung pathology and inflammation in an ovalbumin-induced asthma model in mouse were examined. Materials and Methods:BALB/c mice were divided into three groups: control group (animals were not sensitized), asthma group (animals were sensitized by ovalbumin), asthma+BMSC group (animals were sensitized by ovalbumin and treated with BMSCs). BMSCs were isolated and characterized and then labeled with Bromodeoxyuridine (BrdU). After that the cells transferred into asthmatic mice. Histopathological changes of the airways, BMSCs migration and total and differential white blood cell (WBC) count in bronchoalveolar lavage (BAL) fluid were evaluated. Results:A large number of BrdU-BMSCs were found in the lungs of mice treated with BMSCs. The histopathological changes, BAL total WBC counts and the percentage of neutrophils and eosinophils were increased in asthma group compared to the control group. Treatment with BMSCs significantly decreased airway pathological indices, inflammatory cell infiltration, and also goblet cell hyperplasia. Conclusion:The results of this study revealed that BMSCs therapy significantly suppressed the lung pathology and inflammation in the ovalbumin induced asthma model in mouse