Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China.
CNS Neurosci Ther. 2011 Dec;17(6):590-8. doi: 10.1111/j.1755-5949.2011.00271.x.
To examine the role of increased oxidative stress in the pathogenesis of cerebral infarction in stroke in stroke-prone spontaneously hypertensive rats (SHR-SP).
The differentially expressed brain protein profile was examined in spontaneously hypertensive rats (SHR) (control group) and SHR-SP using two-dimensional fluorescent difference gel electrophoresis (2D-DIGE). In addition, oxidative stress indicators including total antioxidation capacity (TAC), glutathione peroxidase (GPx) activity, and maleic dialdehyde (MDA) were also measured. Lastly, SHR-SP were randomly divided into untreated and treated (vitamins C (200 mg/kg/day) and E (100 mg/kg/day)) groups. After treatment for 4 weeks, half of the animals were sacrificed for detection of TAC, GPx, and MDA. The remaining rats underwent middle cerebral artery occlusion (MCAO) and the infarct areas were measured.
Compared with SHR, the infarct area of SHR-SP was larger (P < 0.01), and the antioxidative proteins including glutathione S-transferase (GST) Pi2 and GST A5 were lower; TAC and GPx activities were decreased and MDA levels. Treatment with vitamins C and E decreased MDA, and increased TAC and GPx activity significantly in SHR-SP, while also decreasing the infarct area (P < 0.01).
Our findings indicate that oxidative stress plays an important role in the pathogenesis of cerebral ischemia.
探讨氧化应激在易卒中型自发性高血压大鼠（SHR-SP）卒中性脑梗死发病机制中的作用。
采用二维荧光差异凝胶电泳（2D-DIGE）技术检测自发性高血压大鼠（SHR）（对照组）和 SHR-SP 的差异表达脑蛋白谱。此外，还测定了氧化应激指标，包括总抗氧化能力（TAC）、谷胱甘肽过氧化物酶（GPx）活性和丙二醛（MDA）。最后，将 SHR-SP 随机分为未治疗组和治疗组（维生素 C（200mg/kg/天）和 E（100mg/kg/天））。治疗 4 周后，一半动物用于检测 TAC、GPx 和 MDA。其余大鼠进行大脑中动脉闭塞（MCAO），测量梗死面积。
与 SHR 相比，SHR-SP 的梗死面积更大（P<0.01），抗氧化蛋白如谷胱甘肽 S-转移酶（GST）Pi2 和 GST A5 水平降低；TAC 和 GPx 活性降低，MDA 水平升高。维生素 C 和 E 治疗可降低 SHR-SP 的 MDA，显著增加 TAC 和 GPx 活性，同时降低梗死面积（P<0.01）。
我们的研究结果表明，氧化应激在脑缺血发病机制中起重要作用。
