杨梅素对小鼠梗死后心肌重塑和心力衰竭的影响及机制

Effects and Mechanism of Myricetin on Postinfarction Cardiac Remodeling and Dysfunction

目的:探讨杨梅素对小鼠梗死后心肌重塑和心力衰竭的影响及调控机制。方法:结扎左冠状动脉前降支建立心肌梗死的模型,将雄性C57/BL6J小鼠随机分为3组(每组20只):假手术组、心肌梗死组、心肌梗死+杨梅素组。心肌梗死+杨梅素组给予杨梅素250 mg/kg/d灌胃,假手术组和心肌梗死组给予同体积5%羧甲基纤维素钠灌胃。药物治疗1月后,小鼠心脏超声检测心功能;Masson染色评估胶原容积分数(collagen volume fraction,CVF);电镜检测心肌线粒体损伤;Western blot检测p-Mst1、LC3和p62的表达。结果:与假手术组相比,心肌梗死组心功能显著降低(P<0.05),心肌ANP和BNP mRNA水平显著增高(P<0.05),CVF显著增高(P<0.05),线粒体明显肿胀,p-Mst1表达和LC3Ⅱ/LC3Ⅰ比率显著增高(P<0.05),p62表达显著降低(P<0.05);与心肌梗死组相比,心功能显著增加(P<0.05),心肌ANP和BNP mRNA水平显著降低(P<0.05),CVF显著降低(P<0.05),线粒体超微结构有显著改善,p-Mst1、p62表达显著降低(P<0.05),LC3Ⅱ/LC3Ⅰ比率显著增高(P<0.05)。结论:杨梅素可能通过抑制Mst1减轻小鼠梗死后心肌重塑和心力衰竭。

Objective： To explore the effects and mechanism of myricetin on postinfaretion cardiac remodeling and dysfunction. Methods： Myocardial infarction （MI） was carried out by the left anterior descending （LAD） coronary artery ligation. Male C57/BL6J mice were randomly divided to three groups （n=20）： sham group, MI group, MI＋ myricetin group. MI＋ myricetin group were given a dose of 250 mg/kg/d myricetin, while sham and MI group received 5% sodium carboxymethyl cellulose gavage. For 1 month, echocardiography was employed to evaluate the cardiac functions. Real-time PCR was used to evaluate the levels of ANP and BNP rnRNA in mice heart. Collagen volume fraction （CVF） was measured by masson staining and changes of mitochondrial ultrastructure were evaluated by trans- mission electron. Western blot was used to determine the expressions ofp-Mstl, LC3 and p62. Results： Compared with sham group, the cardiac functions attenuated significantly （P〈0.05）, with enhanced CVF （P〈0.05） and increased levels of ANP and BNP mRNA （P〈0.05）, as well as evident swollen mitochondria, and the LC3 II/LC3 I ratio and expression ofp-Mstl were upregulated （P〈0.05） and p62 de- J creased （P〈0.05） in sham grou^0.~tpared with those in MI group, the cardiac functions increased significantly （P〈0.05）, with reduced CVF （P〈0.05） and decreased levels of ANP and BNP mRNA （P〈0.05）, as well as restored mitochondrial ultrastructure, and the expres- sions ofp-Mstl and p62 were reduced （P〈0.05） and LC3 II/LC3 I ratio increased （P〈0.05） by the treatment with myricetin in MI ＋ myricetin group. Conclusion： Myficetin can significantly attenuate postinfarction cardiac remodeling and dysfunction, possibly by inhibiting the activation of Mstl.