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

[ Vol. 25 , Issue. 9 ]

Author(s):

Ying Yan, Fei Tong* and Jianer Chen*   Pages 1030 - 1039 ( 10 )

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:

IPC, RES, Bcl-2, Bax, BMP-4/ROS/COX-2, tumor necrosis.

Affiliation:

Department of Rehabilitation Medicine, Zhejiang Chinese Medical University, The Third Clinical Medicine, Hangzhou, Zhejiang, Department of Pathology and Pathophysiology, Provincial Key Discipline of Pharmacology, Jiaxing University Medical College, Jiaxing, Department of Rehabilitation Medicine, Zhejiang Chinese Medical University, The Third Clinical Medicine, Hangzhou, Zhejiang



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