基于线粒体相关内质网膜探讨益气活血方促进心肌梗死大鼠血管新生的作用机制OA

Objective To investigate the effects of Yiqi Huoxue Formula(YQHX)on angiogenesis after myocardial infarction(MI)and to elucidate the underlying regulatory mechanisms involving mitochondria-associated endoplasmic reticulum membranes(MAMs).Methods Thirty male SD rats were randomly divided into sham operation group(n=6)and modeling group(n=24)using a random number table method.The MI model was established by ligating the left anterior descending(LAD)coronary artery.In the sham operation group,the LAD was threaded with a suture without ligation.Following successful modeling,the rats were randomly divided into four groups:model,YQHX low-dose(4.1 g/kg),YQHX high-dose(8.2g/kg),and perindopril(4.0×10-4 g/kg),with six rats per group.Following 28 d of consecutive oral gavage(once daily),all rats were sacrificed and the relevant indices were measured.Cardiac function parameters were evaluated using echocardiography.Serum lactate dehydrogenase(LDH)and endothelin-1(ET-1)levels were measured using ELISA.Histopathological changes and collagen fiber proliferation in myocardial tissues were assessed via HE and Masson staining.Platelet endothelial cell adhesion molecule-1(CD31)expression was detected using immunohistochemistry(IHC).Western blotting(WB)was performed to quantify the protein expression levels of CD31,vascular endothelial growth factor(VEGF),and MAM-associated proteins,including inositol 1,4,5-trisphosphate receptor type 2(IP3R2),glucose-regulated protein 75(GRP75),voltage-dependent anion channel 1(VDAC1),and mitofusin-2(MFN2).Results Compared with the sham operation group,the cardiac function parameters of the model group exhibited significant deterioration,characterized by decreased left ventricular ejection fraction and left ventricular fractional shortening(P<0.05),alongside increased left ventricular end-systolic volume and left ventricular end-diastolic volume(P<0.05).These cardiac function parameters were improved after intervention with YQHX or perindopril(P<0.05).Serum LDH and ET-1 levels increased(P<0.05)in the model group,while decreased in all drug treatment groups using ELISA(P<0.05).Histopathological staining revealed disorganized myocardial arrangement,pronounced inflammatory infiltration,and extensive collagen fiber proliferation in the model group;these pathological alterations were alleviated in all drug treatment groups.IHC result showed that the staining intensity of CD31 in the myocardial tissue of the model group was higher than that of the sham operation group,and this positive expression was further enhanced in all drug treatment groups(P<0.05).WB result showed that the protein expression levels of CD31 and VEGF in the model group were elevated compared to the sham operation group(P<0.05);these levels were further upregulated following drug treatments(P<0.05).Concurrently,IP3R2,GRP75,and VDAC1 expressions were upregulated,whereas MFN2 was downregulated in the model group(P<0.05).All treatment groups reversed the aberrant expression levels of these proteins(P<0.05).Conclusion YQHX exerts a protective effect on cardiac function and myocardial structure following MI.This efficacy is likely attributable to the promotion of angiogenesis and the enhancement of endothelial cell function,which are mediated by the upregulation of CD31 and VEGF,as well as the restoration of the balance of IP3R2,GRP75,VDAC1,and MFN2.