Effect of Buzhong Yiqi Decoction(补中益气汤)on Mechanism of Endoplasmic Reticulum Stress Induced Apoptosis in Cardiac Myocytes of Heart Failure Rats Based on GRP78/CHOP pathway
Objective To investigate the effect of Buzhong Yiqi Decoction(补中益气 汤)on the mechanism of endoplasmic re-ticulum stress-induced apoptosis in heart failure rats.Methods Forty-eight SD rats were grouped,including blank group(12 rats)and model group(36 rats).The blank group was the sham operation group.The model of heart failure(HF)was estab-lished through abdominal aortic constriction surgery in the model group.After successful modeling through abdominal aortic liga-tion,36 rats were divided into model group,trimetazidine hydrochloride group(western medicine group)and Buzhong Yiqi Decoc-tion group,and the rats in each group received the corresponding doses of medication by gavage for 4 consecutive weeks.The con-centration of NT-ProBNP in serum was detected by ELISA.The effect of Buzhong Yiqi Decoction on changes in myocardial tis-sue structure and fibrosis degree was evaluated through HE staining and Masson staining.By using chemical fluorescence meth-od,the content of reactive oxygen species(ROS)in myocardial tissue of heart failure was detected.The degree of myocardial cell apoptosis was evaluated through TUNEL staining.Western blot(WB)was used to detect the protein expressions of endoplasmic reticulum stress-related factors,including CHOP,GRP78,IRE1α,XBP1,PECK,ATF6 and PUMA.Results Compared with that in the blank group,the serum NT-ProBNP value in the model group was significantly higher(P<0.01).Compared with that in the model group,the NT-ProBNP value in the Buzhong Yiqi Decoction group and the western medicine group showed a down-ward trend.Compared with that of the model group,the myocardial tissue of the Buzhong Yiqi Decoction group and the western medicine group was more orderly,with regular morphology,less inflammatory infiltration,reduced edema,less fibrous tissue and narrower space.Compared with that of the blank group,the ROS content in the myocardial tissue of the model group was signifi-cantly increased,and compared with that of the model group,the ROS contents in the myocardial tissue of the Buzhong Yiqi De-coction group and Western medicine group were significantly decreased.Compared with those in the blank group,the cardiomyo-cytes in the model group showed a higher proportion of positive cells after TUNEL staining(P<0.01);the indexes in the Buzhong Yiqi Decoction group and western medicine group changed little.Compared with those in the model group,the TUNEL staining positive cells in the Buzhong Yiqi Decoction group and western medicine group decreased significantly(P<0.01).Com-pared to those in the blank group,the protein expressions of CHOP,GRP78,IRE1α,XBP1,PECK,AFT6 and PUMA in the model group increased significantly(P<0.01).Compared to those in the model group,the protein expressions of CHOP,GRP78,IRE1α,XBP1,PECK,ATF6 and PUMA decreased in the Buzhong Yiqi Decoction group and western medicine group.Conclusion By inhibiting the protein expressions of endoplasmic reticulum stress-related factors(CHOP,GRP78,IRE1 α,XBP1,PECK,ATF6 and PUMA),it can reduce the endoplasmic reticulum stress,delay the process of myocardial remodeling and fibrosis,and then protect the myocardium and improve cardiac function.