卡巴胆碱通过PI3K/AKT信号通路减轻脓毒症大鼠心肌损伤

Abstract

Objective To explore the effect of carbachol on myocardial injury in septic rats, and to further study its influence on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Materials and methods A total of 48 healthy male Sprague-Dawley rats were randomly divided into sham group (n=16), model group (n=16), and carbachol group (n=16). The rat model of sepsis was established via cecal ligation and puncture. Carbachol was intraperitoneally injected (10 μg/kg) immediately after operation in carbachol group, and no cecal ligation was performed in sham group. At 48 h after operation, the survival rate of rats in each group was recorded, the activity of plasma creatine kinase-MB (CK-MB) was detected, and the cardiac function in each group was determined. Moreover, the heart was isolated, and the myocardial tissues were taken to detect the apoptosis level using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) apoptosis kit. The content of inflammatory factors in myocardial tissues was determined using enzyme-linked immunosorbent assay (ELISA) kits, and the expression levels of apoptosis-related proteins and the PI3K/AKT signaling pathway-related proteins were detected via Western blotting. Results Carbachol could significantly raise the survival rate of septic rats (p<0.01), remarkably decrease the activity of CK-MB (p<0.01), markedly reduce the left ventricular internal diameter at end-systole (LVIDs), and markedly increase the left ventricular ejection fraction (LVEF, %) and left ventricular fractional shortening (LVFS, %). Besides, carbachol could evidently lower the apoptosis level of myocardial cells of septic rats (p<0.01), reduce the content of inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 (p<0.01), notably decrease the expression of Caspase-3 in myocardial tissues (p<0.01), remarkably increase the expression of Bcl-2/Bax (p<0.01), and distinctly inhibit