Study On The Mechanism Of Linggui Zhugan Decoction On Endoplasmic Reticulum Stress And Apoptosis In Rats With Heart Failure

Purpose:To observe the effect of Lingguizhugan Decoction on endoplasmic reticulum stress in rats with chronic heart failure,and to provide theoretical basis for clinical application of Lingguizhugan Decoction in the treatment of chronic heart failure Material and method: 45 SPF Rats were randomly divided into blank group(n = 10)and model group(n = 35).Adriamycin(ADR)was injected intraperitoneally to establish chronic heart failure rat model,4mg / kg / W,a total of 6W.30 heart failure rats were randomly divided into four groups: model group(n = 10),captopril group(n = 10),Lingguizhugan Decoction group(Chinese medicine group,n = 10).The dose of traditional Chinese medicine group was 2.79g/kg/d,and that of captopril group was 2.25mg/kg/d.At the end of the experiment,LVEF,lvidd,he and Masson staining were used to observe the pathological changes of cardiac myocytes,TUNEL method was used to detect the apoptosis of cardiac myocytes,Western blot method was used to detect the expression of Er stressrelated proteins.Results :1.Changes of heart structure and function: before drug treatment,LVEF of model rats was less than or equal to 55%,which proved that the model of heart failure was constructed successfully.After drug treatment: the LVEF of model group was significantly lower than that of blank group(P < 0.05),and the lvidd was significantly higher than that of blank group(P < 0.05).After drug intervention,the LVEF of traditional Chinese medicine group and captopril group was significantly higher than that of model group,and the lvidd was significantly lower(P < 0.05).The effect of traditional Chinese medicine group on improving LVEF was better than that of captopril(P < 0.05),but there was no significant difference between the two groups(P > 0.05).2.Comparison of myocardial tissue morphology and structure: compared with the blank group,the cardiomyocytes in the model group were disordered and irregular,and there was obvious deposition of blue stained collagen fibers(P < 0.05);After drug treatment,compared with the model group,the cardiac myocytes in captopril group and traditional Chinese medicine group were arranged relatively orderly,with regular morphology and less blue stained collagen fibers(P < 0.05);the effect of traditional Chinese medicine group on inhibiting myocardial fibrosis was better than that in captopril group(P < 0.05).3.Cardiomyocyte apoptosis: the rate of cardiomyocyte apoptosis in the model group wassignificantly higher than that in the blank group(P < 0.05),and the rate of cardiomyocyte apoptosis in the traditional Chinese medicine group and the captopril group was lower than that in the model group(P < 0.05);the inhibition of cardiomyocyte apoptosis in the traditional Chinese medicine group was better than that in the captopril group(P < 0.05).4.Effect on the marker protein of endoplasmic reticulum stress: Western blot showed that the expression of GRP78,caspase-12 and calpain protein in the model group was significantly higher than that in the blank group(P < 0.05);the expression of GRP78,caspase-12 and calpain protein in the traditional Chinese medicine group and captopril group was lower than that in the model group(P < 0.05);there was no difference between the two groups(P > 0.05).5.The effect of perk-eif2 α-ATF4 / chop endoplasmic reticulum stress signaling pathway:the expression of perk phosphorylation,e IF2 α phosphorylation,ATF4 and chop protein in model group was significantly higher than that in blank group(P There was no significant difference between the two groups(P > 0.05).Conclusion:1.Lingguizhugan decoction can improve the heart function of chronic heart failure rats,inhibit the apoptosis of myocardial cells,reduce myocardial injury and myocardial fibrosis.2.Lingguizhugan decoction can inhibit the stress injury of endoplasmic reticulum in rats with chronic heart failure,and its regulatory mechanism may be related to the down regulation of perk e IF2 α-ATF4 / chop signal pathway.3.Lingguizhugan Decoction and captopril can inhibit the stress of endoplasmic reticulum in rats with chronic heart failure,which may be related to the inhibition of perk e IF2 α-ATF4 /chop signal pathway.