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.