Effect of Linggui Zhugan Decoction on myocardial fibrosis and Lats1/Yap signaling pathway in mice after myocardial infraction
This study aims to investigate the effects of Linggui Zhugan Decoction(LGZGD)on myocardial fibrosis(MF)and the Lats1/Yap signaling pathway in mice after myocardial infarction(MI),exploring its role and mechanism in inhibiting MF.The MI-induced ischemic mouse model was established by left anterior descending coronary artery ligation,followed by continuous intervention for six weeks.Doppler ultrasound imaging-system of small animals was used to detect left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),left ventricular internal diameter at end-systole(LVIDs),and left ventricular internal diameter at end-diastole(LVIDd).Pathological changes in myocardial tissue were observed by HE and Masson staining.Serum levels of creatine kinase isoenzyme MB(CK-MB)and lactate dehydrogenase(LDH)were detected by using ELISA.Myocardial tissue mRNA levels of Lats1,Yap,and connective tissue growth factor(CTGF)were determined by RT-qPCR.Protein expression of alpha-smooth muscle actin(α-SMA),collagen Ⅰ(Col Ⅰ),collagen Ⅲ(Col Ⅲ),tissue inhibitor of metal protease 1(TIMP1),matrix metallopeptidase 2(MMP2),Yap,p-Yap,and n-Yap was determined by Western blot.Compared with the sham group,the model group showed significantly decreased LVEF and LVFS levels,increased LVIDd and LVIDs levels(P＜0.01),disordered arrangement of myocardial cells,partial fracture of myocardial fibers,and massive deposition of collagen fibers.Moreover,serum levels of CK-MB and LDH were significantly increased(P＜0.01),while myocardial tissue mRNA levels of Lats1 were significantly decreased(P＜0.01),and mRNA levels of Yap and CTGF were significantly increased(P＜0.01).Protein expression of α-SMA,Col Ⅰ,Col Ⅲ,MMP2,Yap,and n-Yap was significantly increased(P＜0.01),while protein expression of Lats1,T1MP1,p-Yap,and the ratio of p-Yap/Yap were significantly decreased(P＜0.01).Compared with the model group,after intervention with LGZGD(9.36 g·kg-1),mice showed significantly increased LVEF and LVFS levels,decreased LVIDd and LVIDs levels(P＜0.01),more orderly arrangement of myocardial cells,significantly reduced myocardial fiber fracture and collagen fiber deposition.Serum levels of CK-MB and LDH were significantly decreased(P＜0.01),while myocardial tissue mRNA levels of Lats1 were significantly increased(P＜0.01),and mRNA levels of Yap and CTGF were significantly decreased(P＜0.01).Protein expression of α-SMA,Col Ⅰ,Col Ⅲ,MMP2,Yap,and n-Yap was significantly decreased(P＜0.01),while protein expression of Lats1,TIMP1,p-Yap,and the ratio of p-Yap/Yap were significantly increased(P＜0.01).LGZGD can inhibit MF in mice after MI and improve mouse cardiac function,which is closely related to the activation of the Lats1/Yap signaling pathway.
NETL
NSTL
万方数据
