Effects of chronic peripheral pretreatment with an angiotensin II type-1 receptor blocker on apoptosis-related molecules in rats with cerebral ischemia/reperfusion injury

作     者：Jingping Shi Jingde Dong Jie Lu Yingdong Zhang 

作者机构：Department of Neurology Nanjing Brain Hospital Nanjing Medical University Nanjing 210029 Jiangsu Province China 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2010年第5卷第15期

页      面：1150-1155页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 07[理学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 071003[理学-生理学] 

基　　金：the Science & Technology Planning Project of Nanjing City China No.200801090 

主　　题：angiotensin II cerebral ischemia receptor apoptosis brain-derived neurotrophic factor brain injury neural regeneration 

摘      要：Chronic systemic treatment with blockers of angiotensin II type-1 （AT1） receptors inhibits ischemia-induced apoptosis and reduces ischemic neuronal damage. However, the molecular mechanisms of AT1 receptor blockers in modulating neuronal apoptosis remain poorly understood. Pretreatment with irbesartan significantly suppressed cell apoptosis at 1-7 days following cerebral ischemia/reperfusion, increased levels of brain-derived neurotrophic factor, and elevated the ratios of Bcl-2/Bax and phosphorylated cyclic adenosine monophosphate response element-binding protein （pCREB）/CREB in the ischemic cortex at 1 day after reperfusion, as well as suppressing caspase-3 activation. Cerebral ischemia increased the mRNA expression of AT1 and AT2 receptors in the ischemic cortex, whereas irbesartan blocked this increase in AT1 expression but potentiated the expression of AT2. Therefore, this AT1 receptor blocker was neuroprotective by increasing the ratios of Bcl-2/Bax and pCREB/CREB, increasing brain-derived neurotrophic factor levels, inhibiting caspase-3 activation, and modulating AT receptor expression.