重组血红素氧合酶-1基因腺相关病毒对慢性脑缺血大鼠认知功能的影响  

Effect of heme oxygenase-1 gene on cognitive function during chronic cerebral ischemia in rats

作　　者：王成夭[1] 章军建[2] 王焱林[1] 何祥虎[1] 

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

出　　处：《中华麻醉学杂志》2006年第8期745-748,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金资金(30270483)

摘　　要：目的观察重组血红素氧合酶-1(HO-1)基因腺相关病毒(AAV)对慢性脑缺血大鼠认知功能的影响。方法40只健康雄性SD大鼠,随机分为5组(n=8)：假手术组(SH组)、慢性脑缺血1月组(I1组)、慢性脑缺血3月组(I3组)、基因治疗1月组(G1组)和基因治疗3月组(G3组)。SH组、I1组及I3组大鼠小脑延髓池注射生理盐水10μl,1周后I1组和I3组结扎双侧颈总动脉造成脑缺血,并分别观察1个月或3个月,SH组仅分离颈总动脉不结扎。G1组和G3组小脑延髓池注射重组HO-1基因AAV,1周后结扎双侧颈总动脉,分别观察1个月或3个月。跳台法测试大鼠学习、记忆能力,免疫组化法测定海马HO-1蛋白的表达,逆转录-聚合酶链反应测定海马HO-1 mRNA的表达。结果与SH组比较,I1组、I3组学习、记忆能力下降(P＜0．05),I1组、I3组间差异无统计学意义；G1组学习能力下降(P＞0．05)。G1组学习、记忆能力强于I1组,G3组学习、记忆能力强于I3组(P＜0．05),G1组、G3组间学习、记忆能力差异无统计学意义。SH组、I1组、I3组海马有少量散在的HO-1蛋白表达和HO-1 mRNA(390 bp)基础表达。G1组和G3组海马HO-1蛋白和HO-1 mRNA表达高于SH组、I1组和I3组(P＜0．05)。结论小脑延髓池注射重组HO-1基因AVV可改善慢性脑缺血大鼠的认知功能。Objective To investigate the effect of heme oxygenase-1 （HO-1） gene on cognitive function during chronic cerebral ischemia （CCI）. Methods Forty male SD rats weighing 280-320 g were randomly divided into 5 groups （ n = 8 each） ： group Ⅰ sham operation; group Ⅱ CCI × 1 month; group Ⅲ CCI × 3 month; group Ⅳ CCI ＋ HO-1 gene × 1 month and groupV CCI ＋ HO-1 gene × 3 month. CCI was produced by ligation of bilateral common carotid arteries and observed for 1 month in group Ⅱ and 3 month in group Ⅲ. The adeno-associated virus （AAV） was used to carry HO-1 gene and injected into cerebral-spinal-fluid （CSF） of rats with CCI in group Ⅳ and Ⅴ. Learning and memory ability was evaluated using jumping-platform. 1 month and 3 months after bilateral common carotid arteries the animals were decapitated under pentobarbital anesthesia. The brains were immediately removed and the expression of HO-1 mRNA and protein in hippocampus were detected using RT-PCR and immuno- histochemistry respectively. Results The learning and memory ability of rats at 1 month and 3 months after ligation of bilateral common carotid arteries was significantly lower in group Ⅱ and Ⅲ than in SH group （ P 〈 0.01 ）, but there was no difference in learning and memory ability between group Ⅱ and Ⅲ . Treatment with HO-1 gene significantly improved the learning and memory ability in group Ⅳ and Ⅴ as compared with that in group 1Ⅱand Ⅲ. The expression of HO-1 mRNA and protein was very low in the brains of rats in group SH, Ⅱ and Ⅲ and was significantly increased in group Ⅳ and Ⅴ （ P 〈 0.01 ）. Conclusion HO-1 gene therapy can improve cognitive function of rats with chronic cerebral ischemia.

关 键 词：血红素氧化酶(脱环) 基因疗法 脑缺血 认知 

分 类 号：R749.1[医药卫生—神经病学与精神病学]