利心冲剂通过SIRT3/PFKFB3/HIF-1_(α)信号通路促进心肌梗死后心力衰竭小鼠心肌血管新生的作用机制  

The Mechanism of Lixin Granules on Promoting Myocardial Angiogenesis in Mice with Heart Failure after Myocardial Infarction through SIRT3/PFKFB3/HIF-1_(α)Signaling Pathway

作　　者：陆文江 刘雨辰 高想[2] 苏忆玲 王力 陆齐[1] LU Wenjiang;LIU Yuchen;GAO Xiang;SU Yiling;WANG Li;LU Qi(Affiliated Hospital of Nantong University,Nantong 226001,Jiangsu,China)

机构地区：[1]南通大学附属医院,江苏南通226001 [2]南通市中医院

出　　处：《中西医结合心脑血管病杂志》2022年第8期1392-1399,共8页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

摘　　要：目的通过检测心肌梗死后心力衰竭小鼠心肌组织沉默调节蛋白3(SIRT3)/6-磷酸果糖-2-激酶/果糖-2,6-双磷酸酶3(PFKFB3)/缺氧诱导因子1_(α)(HIF-1_(α))的表达,探讨利心冲剂促进心肌梗死后心力衰竭小鼠心肌血管新生的可能机制。方法将C57BL/6J雄性小鼠结扎左冠状动脉前降支4周建立心力衰竭模型。将小鼠随机分为对照组、模型组、利心冲剂低剂量组(28 g/kg)、利心冲剂高剂量组(56 g/kg)和美托洛尔组(0.06 g/kg),连续给药4周。采用免疫组化CD31染色检测血管密度,蛋白免疫印迹法检测SIRT3、PFKFB3和HIF-1_(α)表达情况。结果与对照组比较,模型组小鼠心脏功能变差,血管新生减少,心肌SIRT3、PFKFB3、HIF-1_(α)蛋白水平下降(P<0.05)。利心冲剂各剂量组小鼠心脏功能明显改善,血管新生增加,心肌SIRT3、PFKFB3、HIF-1_(α)蛋白水平升高(P<0.05),且与剂量成正比。结论利心冲剂可能通过调控SIRT3/PFKFB3/HIF-1_(α)信号通路,促进心肌梗死后心力衰竭小鼠心肌血管新生。Objective To explore the possible mechanism of Lixin Granules on myocardial angiogenesis in mice with heart failure after myocardial infarction by detecting the expressions of silencing regulatory protein 3(SIRT3)/fructose-6-phosphofructose-2-kinase/6-phosphate fructose-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3)/hypoxia inducible factor 1(HIF-1_(α))in myocardial tissue.Methods The anterior descending branch of the left coronary artery of male C57BL/6J mice were ligated for 4 weeks to establish mice model of heart failure.The mice were randomly divided into the control group,model group,Lixin Granules low-dose group(28 g/kg),Lixin Granules high-dose group(56 g/kg),and metoprolol group(0.06 g/kg),all of them were treated for 4 weeks.The vascular density was detected by immunohistochemical CD31 staining,and the protein expressions of SIRT3,PFKFB3 and HIF-1_(α)were detected by Western Blotting.Results Compared with the control group,the cardiac function in the model group was worse,angiogenesis was decreased,and the protein expressions of SIRT3,PFKFB3 and HIF-1_(α)were decreased(P<0.05).The cardiac function,angiogenesis and the protein expressions of SIRT3,PFKFB3 and HIF-1_(α)in myocardium in Lixin Granules groups were increased(P<0.05),which was proportional to the dose.Conclusion Lixin Granules might promote myocardial angiogenesis in mice with heart failure after myocardial infarction by regulating SIRT3/PFKFB3/HIF-1_(α)signaling pathway.

关 键 词：心力衰竭 心肌梗死 利心冲剂 沉默调节蛋白3/6-磷酸果糖-2-激酶/果糖-2 6-双磷酸酶3/缺氧诱导因子1_(α)通路 血管新生 小鼠 实验研究 

分 类 号：R54[医药卫生—心血管疾病]