【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。更多还原

【Abstract】 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) :groupⅠsham operation;groupⅡCCI×1 month;groupⅢCCI×3 month;groupⅣCCI+HO-1 gene×1 month and groupⅤCCI+HO-I gene×3 month.CCI was produced by ligation of bilateral common carotid arteries and observed for 1 month in groupⅡand 3 month in groupⅢ.The adeno-associated virus (AAV) was used to carry HO-1 gene and injected into cerebral-spinal-fluid (CSF) of rats with CCI in groupⅣandⅤ.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 groupⅡandⅢthan in SH group (P＜0.01),but there was no difference in learning and memory ability between groupⅡandⅢ.Treatment with HO-1 gene significantly improved the learning and memory ability in groupⅣandⅤas compared with that in groupⅡand m .The expression of HO-1 mRNA and protein was very low in the brains of rats in group SH,ⅡandⅢand was significantly increased in groupⅣandⅤ(P＜0.01).Conclusion HO-1 gene therapy can improve cognitive function of rats with chronic cerebral ischemia.更多还原