β-blocker propranolol mediates VCAM1 to regulate NF-κB signaling pathway to improve rats with ischemic cardiomyopathy
Objective To establish a rat model of ischemic cardiomyopathy(ICM),to explore whether propranolol can improve the ICM by regulating VCAM1/NF-κB signaling pathway.Methods Fifty SD rats were randomly divided into Control group(control group),ischemic cardiomyopathy group(ICM group),Propranolol group(Propranolol group),propranolol+overexpression control group(Propranolol+ov-NC group)and propranolol+overexpression VCAM1 group(Propranolol+ov-VCAM1 group),with 10 rats in each group.RT-qPCR was used to detect the expression of VCAM1 mRNA in rat myocardial tissue;Western blot was used to detect the expression of VCAM1,p-NF-κB and NF-κB protein in rat myocardium.HE staining was used to observe the pathological changes of myocardial tissue in rats.Masson staining was used to observe the degree of myocardial fibrosis in rats.The ratio of M1/M2 macrophages in rat myocardium was observed by immunofluorescence.The contents of IL-1β,IL-6 and IL-10 in myocardial tissue of rats were detected by ELISA.Results In the control group,the myocardial fibers were arranged neatly,no edema was found in the myocardial interstitium,and almost no collagen fibers were distributed in the myocardium.In ICM group,there were disordered fiber arrangement,interstitial edema and a large number of uneven collagen fibers in the myocardium of rats.Myocardial injury and fibrosis were improved in propranolol group and propranolol+ov-NC group.Myocardial injury and fibrosis in propranolol+ov-VCAM1 group were more serious than those in propranolol group and propranolol+ov-NC group.Compared with the control group,the expression of VCAM1 mRNA and protein and the phosphorylation level of NF-κB in the myocardial tissue of rats in ICM group increased significantly,and the proportion of M1-type macrophages and the contents of IL-1β and IL-6 increased significantly,while the proportion of M2-type macrophages and the content of IL-10 decreased significantly.Compared with ICM group,the expression of VCAM1 mRNA and protein and the phosphorylation level of NF-were arranged neatly,no edema was found in tl group and Propranolol+ov-NC group decreased significantly,while the proportion of M1 type macrophages and the contents of IL-1β and IL-6 decreased significantly,while the proportion of M2 type macrophages and the content of IL-10 increased significantly.Compared with Propranolol group and Propranolol+ov-NC group,the expression of VCAM1 mRNA and protein and the phosphorylation level of NF-κB in myocardial tissue of rats in Propranolol+ov-VCAM1 group increased significantly,while the proportion of M1 type macrophages and the contents of IL-1β and IL-6 increased significantly,while the proportion of M2 type macrophages and the content of IL-10 decreased significantly.Conclusion Propranolol treatment can improve myocardial injury and fibrosis in ICM rats by down-regulating VCAM1 expression,and its mechanism may be related to inhibiting the polarization of M1 macrophages mediated by NF-κB phosphorylation.
万方数据
维普
