rAAV+HO-1基因对慢性脑缺血大鼠认知能力和氧化应激的影响  

Effect of Heme Oxygenase-1 Gene on Cognitive Function and Oxidative Stress During Chronic Cerebral Ischemia in Rats

作　　者：王京[1] 王成夭[1] 章军建[2] 

机构地区：[1]武汉大学中南医院麻醉科 [2]武汉大学中南医院神经内科,湖北武汉430071

出　　处：《武汉大学学报（医学版）》2008年第1期1-4,16,共5页Medical Journal of Wuhan University

基　　金：国家自然科学基金资助项目(编号:30270483)

摘　　要：目的:研究从重组腺相关病毒介导血红素氧合酶-1(rAAV+HO-1)基因对大鼠慢性脑缺血认知能力改变和抗氧化应激作用。方法:成年雄性Wistar大鼠45只,每组各15只,随机分为假手术组(SH)、缺血2月组(2-VO),缺血2月+HO-1治疗组(2-VOH)。各组在脑立体定位仪下定位大鼠海马部位,2-VOH组缓慢注射rAAV+HO-1基因2μl,余组注入等量生理盐水。7 d后,采用永久节扎双侧颈总动脉方法制备慢性脑缺血动物模型。大鼠慢性缺血8周后,Morris水迷宫检测大鼠空间学习能力,Western blotting检测大鼠海马组织HO-1蛋白表达水平的变化,酶学法检测大鼠海马SOD活性、MDA含量、NO水平改变。结果:2-VO组大鼠认知水平下降与SH组比较,差异有统计学意义(P<0.01),2-VOH组比2-VO组逃避潜伏期明显减少,空间探索试验穿过平台次数增多,差异具有统计学意义(P<0.01),2-VOH组HO-1蛋白水平表达与2-VO组对比有统计学差异(P<0.01),2-VOH组与2-VO组对比SOD活性增多、MDA含量和NO水平下降,有统计学差异(P<0.05),2-VOH组与SH组SOD活性、MDA和NO含量无统计学差异(P>0.05)。结论:海马注射重组腺相关病毒介导HO-1基因,能够使慢性脑缺血大鼠海马组织HO-1蛋白水平表达升高,增加SOD活性,降低MDA、NO含量,减少氧化应激损伤,一定程度上改善大鼠空间认知学习能力。Objective： To investigate the effect of heme oxygenase-1 （HO-1） gene transfected by a recombinant adeno-associated virus vector injected in rats hippocampus on cognitive function and oxidative stress during chronic cerebral ischemia（CCI）. Methods： Thirty male Wistar rats were divided into sham operation group （SH）, two-month CCI group （2-VO） and two-month CCI ＋ HO-1 group（2-VOH）. The HO-1 gene was injected into hippocampus in 2-VOH group. Seven days later, CCI was induced by permanent occlusion of bilateral common carotid arteries in rats.Learning and memory ability was evaluated by Morris water maze（MWM）. After 8 weeks, the level of HO-1 protein in hippocampus was determined with Western blotting. SOD and MDA Test Kit was used to test levels of MDA, NO and activities of SOD in hippocampus. Results： The ability of rats at two months after ligation of bilateral common carotid arteries was significantly lower in 2-VO group than that in SH group（P〈0.01）; In the 2-VOH group, the escape latency was significantly shorter than that in 2-VO group （P〈0.01）; The expression of HO-1 protein was very low in SH and 2-VO group, but it was significantly increased in 2-VOH group（P〈 0.01）; SOD activity was up-regulated and MDA, NO levels were down-regulated in the hippocampus in 2-VOH group compared to the 2-VO rats （P〈0.05）. Conclusion： These results indicate that HO-1 gene transfected by a recombinant adeno-associated virus vector can improve rats cognitive function and reduce oxidative stress during chronic cerebral ischemia.

关 键 词：慢性脑缺血 认知功能损害 血红素氧合酶 腺相关病毒 氧化应激损伤 

分 类 号：R749[医药卫生—神经病学与精神病学]