腺病毒介导Nogo受体特异性RNA干扰对大鼠脑缺血再灌注后轴突再生和神经行为的影响

Impacts of adenovirus- mediated RNA interference targeting Nogo receptor on axon regeneration and neurofunctional recovery after cerebral ischemia and reperfusion in rats

目的观察腺病毒介导Nogo受体特异性RNA干扰对大鼠脑缺血再灌注后轴突再生及神经行为的影响。方法采用线栓法制作大鼠缺血再灌注模型，20只大鼠随机分为假手术组、脑缺血再灌注组和RNAi干预组、阴性对照组。术后24h、9周行CT测量脑梗死体积，术后行神经功能评分，示踪技术观察皮质红核束和皮质脊髓束。结果RNAi治疗后脑梗死体积较缺血再灌注组和阴性对照组没有明显变化（P〉0．05），而RNAi治疗3周后，神经功能有明显地恢复（P〈0．01），RNAi治疗9周后健侧皮质红核束发出侧枝支配病灶侧的数量明显增多（P〈0．01）。结论腺病毒介导NgR特异性RNAi可以增加来源于健侧皮质的轴突侧枝出芽，从而促进神经功能的恢复。

Objective To investigate the impact of Adenovirus -mediated RNA interference （RNAi） targeting Nogo receptor（NgR） on the behavior recovery and axon regeneration after experimental stroke in rats. Methods Cerebral ischemia and reperfusion were induced by nylon monofilament. Twenty rats were randomly divided into sham group, cerebral ischemia reperfusion group, adenovirus vector （ Ad - shRNA - NgR ） treatment group （ RNAi intervention group） and adenovirus control vector （ Ad - shRNA - HK ） treatment group （negative control group）. Tomography （CT） was used to measure the infract volume at 24 h and 9 w after cerebral iscbemia reperfusion . Staircase test was used to evaluate the neurofunctional recovery after cerebral ischemia reperfusion. BDA was used to trace corticorubral tract and corticospinal tract to assess the axonal regeneration. Results There was no significantly difference in infarct volume between groups （ P 〉 0. 05 ）, but the behavioral outcomes （ P 〈 0. 01 ）and the numbers of midline crossing fibers projecting to the contralateral red nucleus were increased in Ad - shRNA - NgR treatment group. Conclusion Adenovirus - mediated RNAi targeting NgR could increase the axonal sprouting from the uninjured cerebral cortex and promote neurological recovery.