ABSTRACT
Objective:To investigate the protective effect of spironolactone on myocardial injury in septic rats and to provide a novel measure for the diagnosis and treatment of sepsis myocardial injury.Methods:Totally 120 male Sprague-Dawley rats were randomly divided into the sham group, cecal ligation and perforation group (CLP group), and spironolactone group. The sham group was only exposed to the cecum by laparotomy. CLP was performed to induce sepsis in the CLP group and spironolactone group. The cecal perforation was ligated and the contents of the intestine were squeezed out. The spironolactone group was administered spironolactone by gavage with a dose of 20 mg/(kg·d) per rat. The sham and CLP groups were given the same dose of saline. The experiment period was 7 days. After the rats were sacrificed, blood was collected and myocardial tissue was removed. The changes of serum TNF-α, IL-6, cTnI and CK-MB levels were detected by ELISA. Cardiac structure and function were detected by echocardiography. The relative apoptosis of left ventricular myocytes in rats was detected by TUNEL staining. The levels of TNF-α, IL-6, Bcl2-associated X protein (Bax), B cell lymphoma 2 (Bcl2) and Caspase 3 in the left ventricle tissue were detected by immunohistochemistry.Results:Compared with the CLP group, the levels of TNF-α and IL-6 in serum and left ventricular tissue were significantly decreased ( P<0.05) and serum levels of cTnI and CK-MB were significantly down-regulated ( P<0.05). Heart rate (HR) and left ventricular diastolic dimension (LVDd) were significantly reduced ( P<0.05), and ejection fraction (EF) and left ventricular fractional shortening (FS) increased significantly ( P<0.05). Ventricular muscle apoptosis was improved ( P<0.05),the level of apoptosis-related protein Bcl2 was increased and the Bax and Caspase3 expression were significantly down-regulated ( P<0.05).The expression of Bcl2 protein, EF and FS in the CLP group were significantly lower than those in the sham group( P<0.05), and the remaining indexes were significantly higher than those in the sham group( P<0.05). Conclusions:Spironolactone can treat sepsis-induced myocardial injury by reducing inflammatory response caused by sepsis, reducing myocardial damage, alleviating ventricular muscle apoptosis, and improving ventricular structure and function.