【作者】 王耀羚；

【导师】 赖新生；

【作者基本信息】 广州中医药大学 ， 针灸推拿学， 2010， 博士

【摘要】 目的：阿尔茨海默病(AD),即老年性痴呆,是发生于老年前期或老年期的一类神经退行性病变。其临床特征为严重的学习记忆力下降、分析判断能力衰退、情绪改变以及行为失常。随着社会的发展,世界老龄化问题日益突出,AD将成为影响人类生存质量和生活质量的严重问题。如何防治AD也成为世界广大医学工作者的攻克难关。AD的发病机制复杂,众多的信号分子参与其中,因此,如何明确其发病机制,制定出有效的治疗方案,是现今医学界面临的重大问题。祖国医学在防治老年病方面有独特的疗效和方法,在AD的治疗过程中也显示出良好的治疗效果,中医在治疗AD上,通过长期的实践观察和经验总结,运用中药、针灸、以及针药相结合等多种治疗方法,取得了比较满意的疗效。针灸治疗AD因其疗效显著、作用持久、安全方便等特点备受国内外医学工作者的关注,也因此广为临床工作者采纳和选用。神门穴作为针灸治疗AD的常用效穴,其临床疗效已经有目共睹,但其作用机制和机理还缺乏相应的实验室依据。因此,深入探讨神门穴治疗AD的作用机理,为神门穴以及其它治疗AD的有效穴位的临床疗效判定提供理论支持,提高AD的疗效有重要的意义。本次课题将运用18F-PET脑功能成像技术,分析针刺神门穴对于AD动物脑区的作用区域,比较神门穴的即时治疗效应和疗程后效应的图像区别,通过PET图像资料分析神门穴治疗AD的作用特点。希望通过本次课题,为探讨神门穴治疗AD的作用机制提供强有力的影像学依据,同时也为筛选针灸治疗AD的有效穴位,优化针灸治疗AD的标准化处方提供实验依据。方法：将SD大鼠随机分为三组：正常组、模型组和神门组。模型组和神门组进行基底核损伤造模,D-半乳糖腹腔注射结合双侧大脑Manyert核子注射IBO复合模型。造模完成后在Y迷宫系统中对各组大鼠学习记忆能力进行测试。同时,神门组在针刺神门穴的同时进行PET成像,正常组和模型组在未进行任何处理的情况下也进行PET成像,对照成像结果。造模10天后开始,对神门组进行神门穴的针刺治疗,每次治疗30分钟,每天一次,共20次。正常组和模型组未予以任何治疗处理。治疗完成后三组再次进行PET成像检查,对比检查结果。结果：1、Y迷宫学习记忆能力测试：正常组、模型组和神门组大鼠在治疗前的全天总反应时间,模型组与正常组比较,模型组大鼠的全天总反应时间明显延长,差异有统计学意义(P<0.05)；神门组与模型组相比,全天总反应时间减少,差异无统计学意义(P>0.05)。经过20天的治疗后,模型组与正常组比较,模型组大鼠的全天总反应时间明显延长,差异明显,具有显著的统计学意义(P<0.01)；神门组与模型组相比,全天总反应时间减少,差异有显著的统计学意义(P<0.01)。神门组与正常组相比,全天总反应时间稍长,差异无统计学意义(P>0.05)。比较治疗前后三组的全天总反应时间,可以发现,各组的前后差异并没有统计学意义(P>0.05)。但是,神门组治疗后与模型组相比较,差异有显著统计学意义的(P<0.01)。证明神门穴对于提高AD大鼠学习记忆能力是有显著效果的。2、PET成像：①神门穴针刺的即时效应：神门组在针刺神门穴的同时进行PET成像,而模型组未作任何治疗处理,两组的成像比较,最明显的区别是神门组的纹状体区域出现了高像数反应点。其它区域未见明显高像数反应点。②神门穴针刺的疗程后效应：经过20天未予任何治疗后,正常组与模型组相比,在p<0.001情况下,右缘前皮层、右胼胝体、右带状回、右荚膜、右侧核群、左中隔区、左纹状体、、左第三脑室等多个区域出现了较强反应点。而神门组在经过20天治疗后,与模型组的PET成像对比发现,在p<0.001情况下,皮质运动区、胼胝体、隔区、纹状体、海马区、第三脑室、额眶部以及额皮质联合区都出现了不同程度的较强的反应点。结论：通过行为学测试的实验数据,证明神门穴对于改善AD大鼠的学习记忆力有明显作用。而针刺神门穴PET的即时成像显示,针刺神门穴可以激活AD大鼠脑部的纹状体区域,改善其学习记忆能力。神门穴疗程后的PET成像表明,通过针刺神门穴的治疗,能够刺激大脑多个区域的神经组织。而这些区域功能广泛,既包括运动功能,也包含情绪控制以及学习记忆能力。神门穴治疗AD的机理可能是通过激活这些相关区域以达到改善其功能状态的作用。神门穴的PET即时成像和疗程后成像相比,疗程后AD大鼠大脑内的多个区域出现高像数反应点,与即时成像相比较,高像数反应点明显增多,说明经过20天的针刺神门穴治疗后,AD大鼠脑区的更多区域被激活,由之前的单一的纹状体区变成了包含皮质运动区、胼胝体、纹状体等多个区域的较大范围。而这些区域的功能也各不相同,包括运动功能、情绪控制以及学习记忆能力等多个方面。由此可见,针刺神门穴治疗AD是有效的,而此治疗效果需要一定的疗程时间,针刺神门穴的治疗效应也具有一定的持续性。针对AD的学习记忆力下降、分析判断能力衰退、情绪改变以及行为失常等临床表现,针刺神门穴可以多靶点、多途径、多层次改善大脑多个相关区域的功能状态以达到综合治疗AD的作用,从影像学上进一步证明了神门穴是治疗AD的效穴,为进一步研究经穴治疗AD,筛选针灸治疗AD的有效穴位,优化针灸治疗AD的标准化处方提供实验依据。同时,本次实验也再一次证明了针刺具有多靶点、多途径、多层次的整体疗效和综合效应。更多还原

【Abstract】 Objective:Alzheimer’s disease (AD) is a disease of the old, which is also named senile dementia.it is mainly demonstrateted the symptoms of cognitive handicap of progressive hypomnes ia occurred at the presensium or senectitude, which accompanied by psychological and dystropic neurodegene rative symptoms. Its characteri clinical manifestations is a serious decline in learning and memory function, arialytical judgement capacity of a recession, emotional changes and dystropy, which has seriously affected the daily life and rusult in decline of the quality of patient’s life.The pathogenesis of AD is so complicated because Many signaling molecules have taken part in the process of it.How to make clear The pathogenesis of AD is a most difficult problem the doctors and medical science workers should handle.The traditional chinese medcine has special ways to prevent or treat senile diseases, and it has shown good curative effect on AD’treatment. The traditional chinese medicine treat AD with chinese medcine and acupuncture while senmen point always been used as a effective point during the AD’therapy.But its mechanism of action is not very clear.So the reseach of it is very meanful.We apply the 18F-PET functional image to study the metergasis feature of AD’brain which treated by puncturing senmen ponit, and analysis different point’s various action on the various emcephalic regions. From this, we can choose effective acupoints of AD’treatment, And offer an experimental basement of standard prescription of AD’s treatment.Methods:SD rats were randomly divided into 3 groups:the normal group, puremodle group and senmen group, the puremodle group were made by damage of the basal ganglia and injection of D-galactose in belly and IBO in nucleon. After the modles were made, We used Y maze to test the changes in learning and memory abilities in each group, research their differents refle-ctions.Senmen group has an examination on brain with 18F-PET functional image treatment during needling.and after twenty-day’ acupuncture treatment only in senmen group, three groups were send for 18F-PET functional imaging againResults:1、the results of Y mase examine:before the treatment, Comparing the normal group to puremodle group, the total reaction time of puremodle group rats was longer than the former, there was significance in the two groups (P＜0.05); compared with the puremodle group, the total reaction time of senmen group rats was shorter than the former, there was no significant difference (P＞0.05); after the treatment, Compared with the normal group, the total reaction time of normalgroup rats was shorte than the former, there was significance in the two groups (P＜0.01); and Compared with the puremodle group, the total reaction time of senmen group rats was shorter thanthe former, there was significance in the two groups(P＜0.01).2、PET functional imaging:①the immediatelly effect of senmen acupuncture:Compared with the puremodle group, there was high reactive site in corpus striatum of brains of senmen group.②the curative effect of senmen acupuncture:Compared with the puremodle group, there was various high reactive site in corpus striatum of brains of senmen group, inclnding left Frontal Lobe:Motor Cortex, left Corpus Callosum, Left Limbic System:Septal Area, Leftriatum, Left ocampus, L Third Ventricle, L Frontal Lobe:Orbital Cortex, L Frontal Lobe rontal Asso-ation Cortex.Conclusions:based on the the results of Y mase examine, we can conclude senmen point can improve the ability of learning and memory of AD rats. From the results of the PET imaging, we found senmen point activate several regions of the brain and it improve the function Of the AD’s brain with various ways and targets. comparing the PET imaging immediately and after treatment of the brain of senmen group, much diffrences could be found, after treatment, much more points in the brain were be activated, and the function of these encephalic region were so different, so, it indicated that needling Senmen point can activate several points in the brain and improve their functions, but this function need one course of treatment at least, while, the therapeutic effect could last some time. This experiment also showed acupunture have curative effect on many diseases by multi-target, multi-channel, multi-strata. The experiment offered laboratory evidence on AD, treatment by acupuncture, meanwhile,it also establish the foundament to better acupuncture treatment of AD.更多还原