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机构地区:[1]重庆医科大学药学院药理学教研室,重庆400016
出 处:《基础医学与临床》2011年第11期1229-1233,共5页Basic and Clinical Medicine
基 金:国家自然科学基金(30672211)
摘 要:目的探讨脑缺血/再灌注(I/R)致神经元退行性变所涉及的自由基和SOD2表达的时程变化及其相互关系。方法抽取并回输约40%总血量加双侧颈总动脉夹闭20 min建立I/R损伤模型。组织学检测神经元损伤;Mor-ris水迷宫检测学习记忆能力;分光光度计法检测SOD2活性和丙二醛(MDA)含量;Western blot检测SOD2蛋白表达。结果与假手术组相比,I/R组小鼠学习记忆能力显著降低,海马MDA含量进行性显著升高(P<0.05);I/R术后5、15、30和60 d海马SOD2活性(14.69±2.49 U/mg.pro,14.15±2.41 U/mg.pro,15.07±2.67 U/mg.pro,15.55±2.64 U/mg.pro)和蛋白表达(9.20±1.23,5.40±1.03,4.90±0.92,5.60±0.59)均显著低于假手术组(P<0.05);海马出现进行性神经元核固缩加重和神经元丢失。结论 I/R致小鼠神经元退行性变与SOD2蛋白表达和活性保持低水平状态而氧化应激进行性增强有关。Objective To investigate the changes of time process of SOD2 and free radicals in neurodegeneration induced by cerebral ischemia-reperfusion(I/R).Methods Cerebral I/R model was established through drawing out and reperfusing 40% of the whole blood volume in combination with clamping the carotid arteries for 20 min.Histological observation was performed to evaluate the neural damage;learning and memory ability was examined by Morris water maze;SOD2 activity and malonaldehyde(MDA) were determined by spectrophotometer;and expression of SOD2 was detected by western blot.Results Compared with sham group,the learning and memory ability of I/R group was significantly decreased,the hippocampal MDA level of I/R group was clearly increased in a time-dependent manner(P0.05).SOD2 activity(14.69±2.49 U/mg·pro,14.15±2.41 U/mg·pro,15.07±2.67 U/mg·pro,15.55±2.64 U/mg·pro)and protein expression(9.20±1.23,5.40±1.03,4.90±0.92,5.60±0.59) of 5th d,15th d,30th d,and 60th d I/R group were lower than sham group(P0.05).Histological test indicated there existed the loss and karyopyknosis of neurons in hippocampi of I/R group.Conclusion I/R-induced neurodegeneration may be related to the steady decreases of SOD2 expression and activity and increase of oxidative stress.
关 键 词:缺血/再灌注 神经元退行性变 超氧化物歧化酶-2 自由基
分 类 号:R743.3[医药卫生—神经病学与精神病学]
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