Influence of pachylic acid on myocardial fibrosis in rats with heart failure by regulating PI3K/Akt signaling pathway
Objective To observe the influence of pachymic acid(PA)on myocardial fibrosis(MF)in rats with heart failure(HF)by regulating phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase B(Akt)signaling pathway.Methods A total of 108 rats were randomly separated into 6 groups:18 rats/group:sham group,model group,PA low-dose group(1 mg/kg),PA medium-dose group(5 mg/kg),PA high-dose group(10 mg/kg),and activator group(10 mg/kg PA+0.02 mg/kg PI3K activator 740Y-P).Except for sham group,the other groups were treated with left anterior descending coronary artery ligation to induce HF rat model after myocardial infarction(MI).After successful modeling,the corresponding drugs were in-tragastrically and intraperitoneally injected once a day for 4 consecutive weeks;after 4 weeks,the rat cardiac function was detected by an ultrasound imaging system;HE staining was used to observe the morphology of rat myocardial tissue;Masson staining was used to observe the distribution of rat myocardial collagen and calculate the collagen volume fraction(CVF);hy-droxyproline(HYP)kit was used to determine the content of HYP in rat myocardial tissue;TUNEL staining was used to detect the apoptosis of rat cardiomyocytes;kits were used to detect the levels of reactive oxygen species(ROS),glutathione(GSH),superoxide dismutase(SOD)and malondialdehyde(MDA)in rat myocardial tissue respectively;ELISA method was applied to detect the levels of interleukin(IL)-6 and tumor necrosis factor(TNF)-α in myocardial tissue of rats in each group;Western Blot was applied to measure the expression of Bcl-2-associated X protein(Bax),cysteine protease 3(Caspase-3),transforming growth factor-betal(TGF-β1),Smad2,Smad3,PI3K/Akt signaling pathway proteins in myocardial tissue.Results Compared with sham group,the myocardial tissue structure of the rats in model group was severely damaged,the levels of left ventricular ejection fraction(LVEF),left ventricle fraction shortening(LVFS),GSH and SOD were obviously decreased,the contents of left ventricular end diastolic diameter(LVEDD),left ventricular end systolic diameter(LVESD),CVF,HYP,cardiomyocyte apoptosis rate,and the levels of ROS,MDA,IL-6,TNF-α,Bax,Caspase-3,TGF-β1,Smad2,Smad3,p-PI3K/PI3K,and p-Akt/Akt were obviously increased(P＜0.05);compared with model group,the myocardial tissue damage in PA low,medium and high dose groups was alleviated,the levels of LVEF,LVFS,GSH and SOD were obviously increased,the contents of LVEDD,LVESD,CVF,HYP,cardiomyocyte apoptosis rate,and the levels of ROS,MDA,IL-6,TNF-α,Bax,Caspase-3,TGF-β1,Smad2,Smad3,p-PI3K/PI3K,and p-Akt/Akt were obviously decreased(P＜0.05);compared with PA high-dose group,the levels of LVEF,LVFS,GSH,and SOD in activator group were obviously decreased,the contents of LVEDD,LVESD,CVF,HYP,cardiomyocyte apoptosis rate,and the levels of ROS,MDA,IL-6,TNF-α,Bax,Caspase-3,TGF-β1,Smad2,Smad3,p-PI3K/PI3K,and p-Akt/Akt were obviously increased(P＜0.05).Conclusion PA inhibits myocardial fibrosis in HF rats by inhibiting PI3K/Akt signaling pathway.
万方数据
维普
