Endogenous BMP-4/ROS/COX-2 Mediated IPC and Resveratrol Alleviated Brain Damage

Abstract

The objective of the study was to examine the therapeutic role of combined ischemic preconditioning (IPC) and resveratrol (RES) on brain ischemia/reperfusion injury (BI/RI) by modulating endogenous bone morphogenetic protein-4 (BMP-4)/reactive oxygen species (ROS)/cyclooxygenase-2 (COX-2) in rats. Sprague Dawley (SD) rats were pretreated with 20 mg/kg RES (20 mg/kg RES was administered once a day via intraperitoneal injection 7 days prior to the I/R procedure) and IPC (equal volumes of saline were administered once a day by intraperitoneal injection over 7 days, and the bilateral common carotid arteries were separated for clamp 5 minutes followed by 5 minutes of reperfusion prior to the I/R procedure), and then subjected to 2 hours of ischemia and 22 hours of reperfusion. Blood and cerebral tissues were collected, cerebral pathological injuries and infarct sizes were investigated, serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were measured, the activities of superoxide dismutase (SOD) and ROS were calculated, the contents of methane dicarboxylic aldehyde (MDA), IL-6, TNF-α and hemodynamic change were estimated, and expression levels of b-cell lymphoma-2 (Bcl-2), bcl-2-associated x (Bax), BMP-4 and COX-2 were assessed in cerebral tissues. IPC, RES and a combination of IPC and RES preconditioning ameliorated the pathological damage and infarct sizes, reduced cerebral oxidative stress damage, alleviated inflammatory damage, restrained apoptosis, and downregulated the expression levels of BMP-4 and COX-2 compared with those of the ischemia/reperfusion (I/R) group. This study suggested a combined strategy that could enhance protection against BI/RI in clinical brain disease.

Keywords: BMP-4/ROS/COX-2; Bax; Bcl-2; IPC; RES; tumor necrosis..