摘要
Objective:To investigate the pharmacological mechanism of Qili Qiangxin Capsule(QLQX)improvement of heart failure(HF)based on miR133a-endoplasmic reticulum stress(ERS)pathway.Methods:A left coronary artery ligation-induced HF after myocardial infarction model was used in this study.Rats were randomly assigned to the sham group,the model group,the QLQX group[0.32 g/(kg·d)],and the captopril group[2.25 mg/(kg·d)],15 rats per group,followed by 4 weeks of medication.Cardiac function such as left ventricular ejection fraction(EF),fractional shortening(FS),left ventricular systolic pressure(LVSP),left ventricular end diastolic pressure(LVEDP),the maximal rate of increase of left ventricular pressure(+dp/dt max),and the maximal rate of decrease of left ventricular pressure(–dp/dt max)were monitored by echocardiography and hemodynamics.Hematoxylin and eosin(HE)and Masson stainings were used to visualize pathological changes in myocardial tissue.The m RNA expression of mi R133a,glucose-regulated protein78(GRP78),inositol-requiring enzyme 1(IRE1),activating transcription factor 6(ATF6),X-box binding protein1(XBP1),C/EBP homologous protein(CHOP)and Caspase 12 were detected by RT-PCR.The protein expression of GRP78,p-IRE1/IRE1ratio,cleaved-ATF6,XBP1-s(the spliced form of XBP1),CHOP and Caspase 12 were detected by Western blot.Td T-mediated d UTP nick-end labeling(TUNEL)staining was used to detect the rate of apoptosis.Results:QLQX significantly improved cardiac function as evidenced by increased EF,FS,LVSP,+dp/dt max,-dp/dt max,and decreased LVEDP(P<0.05,P<0.01).HE staining showed that QLQX ameliorated cardiac pathologic damage to some extent.Masson staining indicated that QLQX significantly reduced collagen volume fraction in myocardial tissue(P<0.01).Results from RT-PCR and Western blot showed that QLQX significantly increased the expression of mi R133a and inhibited the m RNA expressions of GRP78,IRE1,ATF6 and XBP1,as well as decreased the protein expressions of GRP78,cleaved-ATF6 and XBP1-s and decreased p-IRE1/IRE1 ratio(P<0.05,P<0.01).Further studies showed that QLQX significantly reduced the expression of CHOP and Caspase12,resulting in a significant reduction in apoptosis rate(P<0.05,P<0.01).Conclusion:The pharmacological mechanism of QLQX in improving HF is partly attributed to its regulatory effect on the mi R133a-IRE1/XBP1 pathway.
基金
Supported by 2022 Science and Technology Innovation Project of Dongzhimen Hospital,Beijing University of Chinese Medicine (No.DZMKJCX-2022-008)。