标题：Tetramethylpyrazine Analogue CXC195 Protects against Cerebral Ischemia/Reperfusion Injury in the Rat by an Antioxidant Action via Inhibition of NADPH Oxidase and iNOS Expression
作者：Liu, Huiqing; Wei, Xinbing; Chen, Lin; Liu, Xiaoqian; Li, Senpeng; Liu, Xinyong; Zhang, Xiumei
作者机构：[Liu, Huiqing; Wei, Xinbing; Chen, Lin; Liu, Xiaoqian; Li, Senpeng; Zhang, Xiumei] Shandong Univ, Sch Med, Dept Pharmacol, Jinan 250012, Shandong, Peo 更多
通讯作者地址：[Zhang, XM]Shandong Univ, Sch Med, Dept Pharmacol, Wenhua West Rd 44, Jinan 250012, Shandong, Peoples R China.
关键词：Tetramethylpyrazine analogue CXC195; Cerebral ischemia/reperfusion;; Reactive oxygen species; NADPH oxidase; Inducible nitric oxide synthase
摘要：Aims: This study was conducted to investigate the protective effects of CXC195, a tetramethylpyrazine analogue, in acute focal cerebral ischemia/reperfusion (I/R) injury in rats and to elucidate the potential mechanism. Methods: Middle cerebral artery occlusion for 2 h followed by reperfusion for 24 h was conducted in male Wistar rats and different doses of tetramethylpyrazine and CXC195 were intraperitoneally injected at 30 min after reperfusion. Results: Our results demonstrated that CXC195 at the dosage of 3 and 10 mg/kg significantly reduced the neurological deficit score and the infarct volume compared to the vehicle-treated group. In addition, CXC195 exhibited a protective effect against hippocampus neuronal cell death and significantly restored the brain ATP content. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and total antioxidative capability (T-AOC), as well as production of malondialdehyde (MDA) and reactive oxygen species (ROS) were assayed in ipsilateral hemisphere homogenates to evaluate the redox status after I/R injury. Treatment with CXC195 significantly attenuated the decrease of SOD, GPx and T-AOC activities and inhibited the elevation of MDA content and ROS generation. Furthermore, CXC195 prevented the upregulation of the NADPH oxidase (NOX) 2 and NOX4, and reduced inducible nitric oxide synthase (iNOS) induction and production of nitric oxide induced by I/R. Conclusion: These results suggest that CXC195 has a neuroprotective effect in transient focal ischemia, which is most likely due to its antioxidant activity by inhibiting NOX and iNOS expression. (C) 2013 S. Karger AG, Basel