首页|注射用益气复脉(冻干)对心肌梗死后慢性心力衰竭的改善作用

注射用益气复脉(冻干)对心肌梗死后慢性心力衰竭的改善作用

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目的 观察注射用益气复脉(冻干)对心梗后心衰小鼠以及OGD诱导的H9C2 细胞损伤的影响.方法 30 只C57BL/6J小鼠随机分为假手术组、模型组、益气复脉组,采用冠脉左前降支结扎法制备心梗后慢性心衰模型,连续给药 4 周.将H9C2 细胞分为正常组、OGD组、益气复脉低、中、高剂量组和JQ1(BRD4 抑制剂)组.心脏超声检测小鼠心功能;HE染色观察心肌组织病理变化;分光光度计检测ATP水平;JC-1法检测线粒体膜电位;RT-qPCR法检测ANP、BNP、BRD4 mRNA表达;TUNEL 法观察心肌细胞的凋亡水平;Western blot 法检测 BRD4、AMPK、p-AMPK蛋白表达.结果 与假手术组比较,模型组小鼠心功能降低(P<0.01),心肌细胞增大,排列不规则,心肌组织ANP、BNP、BRD4 mRNA表达升高(P<0.01),心肌细胞凋亡率升高(P<0.01),心肌组织p-AMPK/AMPK蛋白表达降低(P<0.01),BRD4 蛋白表达升高(P<0.01);与模型组比较,益气复脉组以上指标均有改善(P<0.05,P<0.01).在H9C2 细胞中,与正常组比较,OGD组ANP、BNP、BRD4 mRNA表达升高(P<0.01),H9C2 细胞凋亡率升高(P<0.01),p-AMPK/AMPK蛋白表达降低(P<0.01),BRD4 蛋白表达升高(P<0.01),线粒体膜电位和ATP水平降低(P<0.01);与OGD组比较,益气复脉各剂量组和JQ1 组以上指标均有改善(P<0.05,P<0.01).结论 注射用益气复脉(冻干)具有改善心梗后慢性心力衰竭小鼠心功能,改善心肌细胞线粒体功能和能量代谢的作用,其机制可能与BRD4/AMPK介导的信号通路相关.
Effects of Yiqi Fumai Lyophilized Injection on improving chronic heart failure after myocardial infarction
AIM To observe the effects of Yiqi Fumai Lyophilized Injection on a mouse model of chronic heart failure after acute myocardial infarction and H9C2 cells with injury induced by oxygen and glucose deprivation.METHODS Thirty C57BL/6J mice were randomly divided into the sham-operation group,the model group,and the Yiqi Fumai group,among which the chronic heart failure model was made by ligation of anterior descending coronary artery and given 4 weeks corresponding drug administration.The H9C2 cells were divided into the normal group,the OGD model group,the low-dose,medium-dose and high-dose Yiqi Fumai groups,and the JQ1(BRD4 inhibitor)group.The following detections were conducted:heart ultrasound among the mice;the HE staining of the myocardial tissue for the observation of the morphological changes,spectrophotometry of cellular ATP level,JC-1 method for the determination of the mitochondrial membrane potential,RT-qPCR for the assessment of the mRNA expressions of ANP、BNP and BRD4,TUNEL method for the determination of level of cardiomyocytes apoptosis,and Western blot for the determination of the protein expressions of BRD4,AMPK and p-AMPK in both the mice and H9C2 cells.RESULTS Compared with the sham-operation group,the model group displayed decreased heart function(P<0.01);obviously more hypertrophic or morphologically irregular cardiomyocytes;up-regulated mRNA expressions of ANP,BNP and BRD4(P<0.01);increased cardiomyocyte apoptosis rate(P<0.01);decreased p-AMPK/AMPK protein expression(P<0.01);and increased BRD4 protein expression(P<0.01).Compared with the model group,the Yiqi Fumai groups shared improvement in terms of all the aforementioned indices levels(P<0.05,P<0.01).Compared with the H9C2 cells of the normal group,those of the OGD model group displayed up-regulated mRNA expressions of ANP,BNP and BRD4(P<0.01);increased apoptosis rate(P<0.01);decreased p-AMPK/AMPK protein expression(P<0.01);increased BRD4 protein expression(P<0.01),and decreased mitochondrial membrane potential and ATP levels(P<0.01).Compared with the OGD model group,the groups treated with either Yiqi Fumai or JQ1 demonstrated improvement in terms of the aforementioned indices levels(P<0.05,P<0.01).CONCLUSION Yiqi Fumai Lyophilized Injection exhibits its efficacy in improving cardiac function,myocardial energy metabolism,intracellular mitochondria dysfunction and biogenesis in a mouse model of chronic heart failure after myocardial infarction.The effects may be mediated by regulation of BRD4/AMPK signaling pathway.

Yiqi Fumai Lyophilized Injectionacute myocardial infarctionheart failureenergy metabolismAMPKBRD4

李湘玲、李益萍、高俊杰

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上海中医药大学附属曙光医院,国家中医心血管病临床医学研究中心分中心,上海 201203

注射用益气复脉(冻干) 心肌梗死 心力衰竭 能量代谢 AMPK BRD4

上海市科委重点实验室建设项目(医疗类)上海市科委引导类项目上海市卫生计生委中医药事业发展三年行动计划上海市临床重点专科建设项目

14DZ227320019401934300ZY2018-2020-CCCX-2003-07shslczdzk05301

2024

中成药
国家食品药品监督管理局,信息中心中成药信息站,上海中药行业协会

中成药

CSTPCD北大核心
影响因子:1.217
ISSN:1001-1528
年,卷(期):2024.46(5)
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