Colchicine Promotes Cardiac Function in Rats with Acute Myocardial Infarction by Activating PI3K/AKT/eNOS Signaling Pathway
Objective:To investigate the effect of colchicine on cardiac function in rats with acute myocardial infarction(AMI)by regulating phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/endothelial nitric oxide synthase(eNOS)signaling pathway.Methods:There were 78 rats,12 were randomly selected as the sham-operated group,and the remaining 66 rats were used to construct an AMI model.Rats with successful modeling were divided into model group,colchicine group[4 mg/(kg·d)],and colchicine[4 mg/(kg·d)]+ LY294002(20 mg/mL)group,colchicine[4 mg/(kg·d)])+MK-2206(60μg/mL)group,colchicine[4 mg/(kg·d)]+L-NAME(1.6 mg/mL)group,with 12 rats in each group.Echocardiography was applied to measure left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),ejection fraction(EF),and short-axis shortening(FS)in rats.Rats were sacrificed,and hematoxylin-eosin(HE)staining was used to measure the pathological changes in rat myocardial paraffin sections.Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling(TUNEL)method was implemented to measure cardiomyocyte apoptosis rate.Enzyme-linked immunosorbent assay(ELISA)method was implemented to measure the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6,creatine kinase-MB(CK-MB)in rat serum and superoxide dismutase(SOD),malondialdehyde(MDA),and catalase(CAT)in myocardial tissue homogenate.Western Blot was performed to determine the protein expression of PI3K/AKT/eNOS pathway in rat myocardial tissue.Results:Compared with sham-operated group,the LVESD,LVEDD,serum CK-MB,TNF-α,IL-6 levels,myocardial homogenate MDA,and myocardial cell apoptosis rate in model group increased,and the EF,FS levels,myocardial homogenate SOD,CAT,myocardial tissue p-PI3K/PI3K,p-AKT/AKT,and p-eNOS/eNOS decreased(P<0.05).compared with model group,the LVESD,LVEDD,serum CK-MB,TNF-α,IL-6 levels,myocardial homogenate MDA,and myocardial cell apoptosis rate in colchicine group decreased,and the EF,FS levels,myocardial homogenate SOD,CAT,myocardial tissue p-PI3K/PI3K,p-AKT/AKT,and p-eNOS/eNOS increased(P<0.05).Compared with colchicine group,the LVESD,LVEDD,serum CK-MB,TNF-α,IL-6 levels,myocardial homogenate MDA,and myocardial cell apoptosis rate in colchicine+LY294002 group,colchicine+MK-2206 group,and colchicine+L-NAME group increased,and the EF,FS levels,myocardial homogenate SOD,CAT,myocardial tissue p-PI3K/PI3K,p-AKT/AKT,and p-eNOS/eNOS decreased(P<0.05).Conclusion:Colchicine may exert some protective effect on cardiac function in AMI rats by activating the PI3K/AKT/eNOS pathway.
万方数据
维普
