Effect of Jiangtang Shuxin Recipe(降糖舒心方)on Cardiomyopathy in Diabetes Rats by Inhibiting Endoplasmic Reticulum Stress-Hyperautophagy
Objective:To explore the mechanism of Jiangtang Shuxin(JTSX)recipe in regulating the hyper-activation of autophagy,and reveal its mechanism of preventing myocardial remodeling in diabetic heart failure.Methods:The 100 rats were randomly divided into model group,Western medicine group,low-dose JTSX group(JTSX1),high-dose JTSX group(JTSX2),and sham-operation group using a random number table method,with 20 rats in each group.The diabetic model was first established by intraperitoneal injection of streptozotocin in rats,and then the chronic heart failure was modeled by abdominal aortic coarctation.Each medication group was given corresponding drugs by gavage,while rats in sham-operation group and model group were given equal volume distilled water by gavage once a day for two consecutive months.The 1eft ventricular ejection fraction(LVEF),interventricular septal depth(IVSd),interventricular septal thickness at end-systole(IVSs),left ventricular posterior wall systole(LVPWs)and 1eft ventricular posterior wall diastole(LVPWd)were tested.The HE staining was used to detect myocardial pathology,and the ultrastructural changes of myocardial autophagy were observed by transmission electron microscopy.The transcription of glucose-regulated protein78(GRP78)mRNA,Inositol-requiring enzyme 1(IRE-l)mRNA and tumor necrosis factor receptor-associated factor 2(TRAF2)mRNA were tested by reverse-transcription polymerase chain reaction(RT-PCR),and the autophagy protein of microtubule-associated protein light chain-Ⅱ(LC3-Ⅱ)and Beclin1 were detected by Western blotting.Results:Compared with the model group,the LVPWs,LVPWd,IVSs and IVSd decreased in medication groups,while the LVEF increased in medication groups,with statistically significant difference(P<0.05);The scores of pathological changes in myocardial tissue were significantly reduced in medication groups(P<0.05);The degree of myocardial cell damage has been reduced in medication groups,with autophagosomes,vacuoles and fibrosis decreased;The relative transcription levels of GRP78 mRNA,IRE-1 mRNA and TRAF2 mRNA in myocardial tissue declined significantly in medication groups(P<0.05);The LC3-Ⅱ and Beclin 1 were decreased in medication groups(P<0.05).Compared with the Western medicine group,LVEF significantly increased in JTSX2 group(P<0.05);The scores of pathological changes in myocardial tissue were significantly reduced in JTSX1 group and JTSX2 group(P<0.05);The number of myocardial cells is relatively large,with a decrease in autophagosomes and vacuoles,and a reduction in fibrous proliferation;The relative expression levels of GRP78 mRNA,IRE-1 mRNA,and TRAF2 mRNA in myocardial tissue were significantly reduced in JTSX1 group and JTSX2 group(P<0.05);The relative expression levels of LC3-Ⅱ and Beclin 1 proteins were significantly reduced JTSX1 group and JTSX2 group(P<0.05).Compared with JTSX1 group,JTSX2 group have orderly arrangement of myocardial myofibrils,with less interstitial hyperplasia,mostly smooth and intact cell bodies,and fewer of autophagosomes and vacuoles in cells.All indicators were dose-dependent.Conclusion:Endoplasmic reticulum stress autophagy plays an important role in the occurrence and development of heart failure.Excessive autophagy in diabetes can reduce the number of myocardial cells and damage the ventricular wall.JTSX can alleviate excessive autophagy in myocardial cells,inhibit myocardial remodeling,and improve cardiac function.
万方数据
维普
