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运动训练与电针治疗对脑缺血再灌注大鼠神经可塑性和脑卒中患者功能改善的作用

Role of Exercise Training and Electroacupuncture on the Neural Plasticity of Rats after Cerebral Ischemia-reperfusion and the Functional Improvement of Stroke Patients

【作者】 陆敏

【导师】 张苏明;

【作者基本信息】 华中科技大学 , 神经病学, 2007, 博士

【摘要】 第一部分强化运动训练对脑缺血再灌注大鼠运动功能以及MAP-2和GFAP表达的影响目的探讨应用常规和强化运动训练对脑缺血再灌注大鼠运动功能以及海马区和梗塞灶周围微管相关蛋白-2(MAP-2)和胶质纤维酸性蛋白(GFAP)表达的影响。方法采用大鼠局灶性脑缺血再灌注模型,大脑中动脉阻塞1h,再灌注7、14和21d,54只造模成功的大鼠随机分为造模对照组(A组)、常规运动训练组(B组)和强化运动训练组(C组),分别采用姿势反射试验、肢体不对称应用试验和角落试验观察各组大鼠的运动功能,应用免疫组织化学方法分别检测各组大鼠缺血侧海马区和梗塞灶周围MAP-2和GFAP的表达情况。结果3组实验大鼠的3项行为学测试评分在造模后24h均无明显差异,但在7、14和21d时则有一定差异,与A组比较,除造模后21d时B组角落试验评分外,B组和C组3项测试评分在造模后7d(P<0.05)、14d(P<0.05或0.01)和21d(P<0.05或0.01)均明显好于A组;与B组比较,除造模后21d肢体不对称应用试验评分外,C组评分在14d和21d均明显好于B组(P<0.05)。MAP-2和GFAP的免疫组化结果显示,与A组比较,B组和C组在海马区和梗塞灶周围MAP-2表达的光密度值在14d(P<0.05)和21d(P<0.01)时,GFAP表达的光密度值在7d(P<0.05)、14d(P<0.05)和21d(P<0.01)时均明显高于A组,而且C组MAP-2和GFAP表达的光密度值在14d(P<0.05或0.01)和21d时(P<0.05)也明显高于B组。结论运动训练可促进脑缺血再灌注大鼠运动功能的恢复,其机制可能与脑内MAP-2和GFAP水平上调有关,强化运动训练的效果更明显。第二部分运动训练结合电针治疗对脑缺血再灌注大鼠海马齿状回区Nestin表达的影响目的探讨应用运动训练结合电针治疗对脑缺血再灌注大鼠海马齿状回区巢蛋白(Nestin)表达的影响。方法54只Wistar大鼠随机分为造模对照组(A组)、运动训练组(B组)和运动训练结合电针治疗组(C组),采用大鼠局灶性脑缺血再灌注模型,大脑中动脉阻塞1h,再灌注7、14和21d,应用免疫组织化学方法分别检测各组大鼠缺血侧和对侧海马齿状回区Nestin的表达情况。结果3组大鼠均表现为7d时的海马区Nestin阳性细胞最多,而且在各时间点缺血侧海马DG区的Nestin阳性细胞数均明显多于对侧DG区(P<0.01)。7、14和21d时,C组和B组大鼠缺血侧海马区Nestin阳性细胞较A组明显增多,有显著性差异(P<0.01)。C组大鼠缺血侧海马区Nestin阳性细胞在7d和14d时较B组亦明显增多(P<0.01)。结论脑缺血再灌注大鼠海马区Nestin阳性细胞的增多存在时间规律及原位增殖特性,运动训练和电针治疗可显著增强Nestin阳性表达的数量。第三部分运动训练的训练时间和患者的治疗参与性对脑卒中患者功能预后的影响目的探讨运动训练的训练时间和患者的治疗参与性对脑卒中患者功能预后的影响。方法将60例脑卒中患者随机分为常规训练组(A组)和强化训练组(B组)各30例,两组患者均接受运动训练,但A组患者每次运动训练的训练时间为30-45min,B组患者每次运动训练的训练时间为45-60min。所有患者在入院时和治疗4周后进行功能独立性评定量表(FIM)中的运动功能评定,同时每次运动训练时通过Pittsburgh康复参与量表(PRPS)记录患者的治疗参与情况。结果A组和B组治疗前FIM运动功能平均得分无显著性差异,但两组患者治疗后FIM运动功能平均得分有明显差异,B组患者的FIM运动功能平均得分明显高于A组患者(P<0.05),B组治疗前后FIM运动功能得分改变值明显高于A组(P<0.01) ,而且A组(r=0.787, P<0.01)和B组(r=0.573, P<0.05)患者PRPS评分均与治疗前后FIM运动功能得分的改变值明显相关。结论运动训练时间能够对脑卒中患者的近期运动功能的改善产生影响,患者的主动参与性亦能明显影响其功能预后。第四部分运动训练结合电针治疗对脑卒中偏瘫患者功能改善的临床研究目的探讨运动训练结合电针治疗对不同病程脑卒中患者功能状况的影响。方法将50例急性脑卒中随机分为康复组和对照组各25例,两组患者药物治疗基本相同,康复组同时还接受运动训练和电针治疗,所有患者在治疗前、病程1、3和6月时各进行1次功能评定,采用简式Fugl-meyer运动功能评定(S-FMMFA)、Barthel指数评定(BI)、世界卫生组织生存质量测定简式量表中文版(WHOQOL-BREF)和功能综合评定量表(FCA)分别评定患者运动功能、日常生活活动能力、生活质量以及综合功能状况。结果治疗前和病程1月时两组患者各项评分无显著性差异,康复组患者S-FMMFA(P<0.01)、BI评分(P<0.01)和WHOQOL-BREF量表的生理、心理和环境领域评分(P<0.05)以及生活质量和健康状况主观评分(P<0.05或0.01)在病程3月和6月时明显高于对照组,FCA评分在病程6月时亦明显高于对照组(P<0.01)。结论早期运动训练结合电针治疗能有效改善运动功能,明显提高生活自理能力和生活质量,而维持性康复治疗则继续改善患者功能状况,并最终提高患者的整体功能。

【Abstract】 PartⅠEffects of intensive exercise training on motor function and the expression of MAP-2,GFAP in rats after cerebral ischemia-reperfusionObjective To explore the effects of conventional and intensive exercise training on motor function and the expression of MAP-2 , GFAP in the hippocampus and around the cerebral infracted area of rats after cerebral ischemia-reperfusion.Methods The middle cerebral artery occlusion (MCAO) models was used.The middle cerebral arteries(MCA) of rats were occluded for 1 hour, then reperfused for 7,14 and 21 days. Fifty-four MCAO model-rats were randomized into a control group(Group A), a conventional exercise training group(Group B) and an intensive exercise training group(Group C). Neurologic functional behavior tests (postural reflex test, limb use asymmetrical test and corner test) were performed to test motor function. Immunohistochemistry was used to detect the expression of MAP-2, GFAP in the hippocampus and around the cerebral infracted area of rats.Results Except on the 24h after cerebral ischemia-reperfusion, there were some differences of neurological function behavior tests’scores in three groups on the 7th, 14th and 21th day. The scores of Group B and C, except the score of corner test of Group B on the 21th day, were significant better than that of Group A on the 7th(P<0.05), 14th (P<0.05 or 0.01)and 21th day(P<0.05 or 0.01). The scores of Group C, except the score of limb use asymmetrical test of Group C on the 21th day, were significant better than that of Group B on the 14th and 21th day(P<0.05). In the hippocampus and around the cerebral infracted area of rats, significant increase of MAP-2 immunoreactivity on the 14th day(P<0.05) and 21th day (P<0.01)and GFAP immunoreactivity on the 7th(P<0.05),14th (P<0.05)and 21th day (P<0.01)were detected in Group B and C , compared with that of group A. Significant increase of MAP-2 and GFAP immunoreactivity of Group C were detected on the 14th (P <0.05 or 0.01)and 21th day(P<0.05), compared with that of Group B.Conclusion Exercise training can promote motor functional recovery. The function enhancement may be partially due to the upregulation of MAP-2 and GFAP. Intensive exercise training is more effective.PartⅡEffects of exercise training combined with electroacupuncture on the expression of Nestin in the hippocampus dentate gyrus after cerebral ischemia-reperfusionObjective To explore the effects of exercise training combined with electro- acupuncture on the expression of Nestin in the hippocampus dentate gyrus(DG) after cerebral ischemia-reperfusion.Methods Fifty-four Wistar rats were randomly divided into control group (Group A), exercise training group (Group B), and exercise training combined with electroacupuncture group (Group C). The middle cerebral arteries (MCA) of rats were occluded for 1 h, then reperfused for 7, 14 and 21 days. Immunohistochemistry was used to detect the expression of Nestin in the hippocampus dentate gyrus of rats. Results There was the largest number of Nestin-positive cells in the DG in all groups on the 7th day after cerebral ischemia-reperfusion. Nestin-positive cells in ipsilateral DG were significantly more than those in the counter part at different time points (P<0.01). Significant increase of Nestin expression were detected in rats of Group B and Group C at different time points after cerebral ischemia-reperfusion, compared with that of Group A(P<0.01). We also found that Nestin-positive cells of Group C were significantly more than those of Group B in ipsilateral DG on the 7th day and 14th day after cerebral ischemia-reperfusion(P<0.01).Conclusion The increase of Nestin-positive cells in the DG existed time-regularity and in situ proliferation characteristic after cerebral ischemia- reperfusion. Exercise training and electroacupuncture can significantly promote the expression of Nestin.PartⅢEffects of training time of exercise training and rehabilitation participation of patients on the functional prognosis in stroke patientsObjective To explore the effects of training time of exercise training and rehabilitation participation of patients on the functional prognosis in Stroke Patients. Methods Sixty stroke patients were assigned to the conventional rehabilitation group (Group A) and the intensive rehabilitation group(Group B) randomly. There were 30 patients in each group. The patients in two groups were both received exercise training. The training time of Group A was 30-45 min/d, Group B was 45-60min/d. The Motor Function of Function Independence Measure (FIM) was used to assess motor comprehensive function at pre-therapy and 4 weeks after training. The rehabilitation participation of all patients was evaluated through the Pittsburgh Rehabilitation Participation Scale (PRPS) after every motor training.Results There were no significant differences between FIM motor function scores of two groups before therapy. But FIM motor function scores of Group B were significant higher than that of Group A after training (P<0.05), and FIM motor function scores change between pre-therapy and 4 weeks after training in Group B were significant higher than that in Group A (P<0.01). And the scores of PRPS in Group A (r=0.787, P<0.01) and Group B (r=0.573, P<0.05) were significantly related with FIM motor function scores change between pre-therapy and 4 weeks after training.Conclusion The training time of exercise training can effect the improvement of immediate motor function of stroke patients;The rehabilitation participation of patients also effect significantly the patients’functional prognosis.PartⅣClinical research of exercise training and electroacupuncture on the therapeutic effects in hemiplegia patients with strokeObjective To explore the effects of exercise training and electroacupuncture on the functional outcomes in hemiplegia patients with stroke at different time.Methods Fifty acute stroke patients were assigned to the rehabilitation group (25 cases) and control group (25 cases) randomly. The drug treatments in two groups were almost the same. The patients in rehabilitation group were received exercise training and electroacupuncture. Simplified Fugl-meyer Motor Functional Assessment (S-FMMFA), Barthel Index (BI), the WHO Quality of Life-brief version (WHOQOL-BREF) and Functional Comprehensive Assessment Scale (FCA) were used to assess motor function, ADL, QOL and comprehensive function at pre-therapy and 1, 3 and 6 months after the onset of stroke.Results The Scores in both rehabilitation and control groups were similar at pre-therapy and 1 months after the onset of stroke. The patients in the rehabilitation group at 3 and 6 months demonstrated much higher scores in S-FMMFA(P<0.01), BI(P<0.01) and in physical, psychological, environmental domains(P<0.05), the subjective QOL and health items of WHOQOL-BREF(P<0.05 or 0.01) than those in the control group. The FCA scores in the rehabilitation group at 6 months were also higher than those in the control group(P<0.01).Conclusion Early exercise training and electroacupuncture can effectively improve motor function, ADL and QOL of stroke patients. The continuing rehabilitation therapy is helpful for improving the patients’comprehensive function.

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