Objective Previous studies have showed that TLR4 (Toll-like receptor 4) may trigger apoptosis of cardiomyocytes under conditions of cardiac inflammation and oxidative stress. Studies also presented that oxidative stress played an important role in the development of diabetic cadiomyopathy. Selenium (Se) is an essential trace element which is known as an antioxidant agent. This work aimed to investigate the cadioprotective effect and the possible mechanism of sodium selenite treatment in experimental diabetic rats.
Methods Diabetes was induced in SD rats using intraperitoneal injections of streptozotocin (STZ). Rats were divided into four groups: nondiabetic rat group, nondiabetic rats received sodium selenite (Se) intraperitoneally for 3 weeks, diabetic rats received Se (DMSe group) intraperitoneally for 3 weeks and the diabetic rats were injected saline intraperitoneally for 3 weeks. Myocardial apoptosis was detected using TUNEL assay, TLR4 and caspase-3 expression was measured by RT-PCR and western-blot, left ventricular functions was examined by cardiac catheterization, NADPH activity and intracellular reactive oxygen species (ROS) were also assessed.
Results After treatment with STZ, the rats developed diabetes evidenced by hyperglycemia. Compared with nondiabetic rats, myocardial apoptosis was detected in rat with hyperglycemia, and then left ventricular data demonstrated a significant depression in the left ventricular developed pressure (LVDP) measurement. Mechanistically, significantly increased expression of TLR4 and caspase-3 in myocardial tissue was observed, meanwhile, increased NADPH oxidase activity and ROS production was also detected in rats with hyperglycemia. In contrast, treatment of Se significantly reduced hyperglycemia up-regulated TLR4 and caspase-3 expression, minimised apoptosis in myocardial tissues, and inhibited NADPH oxidase activity and ROS production. Furthermore, the diabetic rats with Se treatment eventually showed greater improvement of LVDP compared to the untreated diabetic rats.
Conclusions We concluded that hyperglycemia induces TLR4 expression in cardiac tissue; Se may act effectively against hyperglycemia-induced cardiac apoptosis as an antioxidant by modulating TLR4 signalling.