强制性运动疗法对脑缺血后大鼠神经功能重塑的影响及机制探讨

Effect of constraint-induced movement therapy on neuronal plasticity of rats after focal cerebral ischemia

目的观察强制性运动疗法对脑缺血后大鼠神经功能重塑的影响,并探讨其机制。方法将90只健康SD大鼠随机分为假手术组、模型组、运动疗法组各30只,3组大鼠均用3.5%水合氯醛1 mL/kg腹腔麻醉,取左侧颈部直切口,分离左颈总动脉、颈内动脉、颈外动脉(ECA),电凝ECA分支,离断ECA。假手术组到此步为止,模型组、运动疗法组制备左侧大脑中动脉闭塞模型;脑缺血模型成功后7 d,运动疗法组建立强制性运动疗法模型。参照改良的Bederson氏6级评分标准对各组大鼠进行神经功能缺损评分,采用原位杂交检测缺血侧大脑皮质及梗塞灶边缘区Nogo受体(NgR)及轴突再生脑源性神经营养因子(BDNF)mRNA,免疫印迹检测NgR、BDNF蛋白。结果与模型组比较,运动疗法组在制模后2、4、8周神经功能缺损评分明显降低,NgR mRNA及蛋白表达降低,BDNF mRNA及蛋白表达升高(P均<0.01)。结论强制性运动疗法可以明显改善大鼠脑缺血后神经功能,其机制可能与下调NgR的表达、上调BDNF表达,从而促进神经功能重塑有关。

Objective To observe the effect of constraint-induced movement therapy （CIMT） in improving the neural plasticity of rats after focal cerebral ischemia and to investigate its mechanism.Methods A total of 90 Healthy SD rats were randomly divided into 3 groups,30 in each group：the sham group,MCAO model group and CIMT group.All rats in 3 groups were intraperitoneally anesthetized by 3.5％ chloral hydrate （1mL/kg）.Through a straight incision in neck,the left common carotid artery,internal carotid artery and external carotid artery （ECA） were separated,and then ECA was ligated and its all branches were electro-coagulated.It was all for rats in the sham group.Rats in the model group and CIMT group were modeled as left middle cerebral artery occlusion （MCAO）,and seven days later CIMT models were made in the CIMT group.The neurological deficit scores of all rats were evaluated by modified Bederson＇s method.The expression of Nogo receptor （NgR） and brain-derived neurotrophic factor （BDNF） mRNA was detected by in situ hybridization histochemistry technique,and protein expression of NgR and BDNF was detected by Western blotting.Results Compared with the model group,the scores of neurological deficit and the expression of NgR mRNA and protein were significantly lower but the expression of BDNF mRNA and protein was higher in the CIMT group at week 2,4 and 8 （all P ＜ 0.01）.Conclusion CIMT could significantly improve neurological function of rats after cerebral ischemia,whose mechanism is closely related to the down-regulation of NgR expression and up-regnlation of BDNF expression,thus to improve neural plasticity.