【作者】 顾建钦；

【导师】 林家瑞；

【作者基本信息】 华中科技大学 ， 生物医学工程， 2004， 博士

【摘要】 痴呆是由于脑功能障碍而产生的获得性智能损害综合症。随着我国人口的老龄化,老年期痴呆的发病率有升高趋势,已成为一个日益突出的社会及医学问题,为此,寻求痴呆的治疗,对改善老年人的生活质量尤为重要,在治疗方面,由于痴呆是器质性病变,绝大多数是不可逆的,所以目前尚无满意的疗效,针对痴呆本质上的治疗仍在努力的探索之中,有些原因所致的痴呆试验性药物治疗取得了一些可喜的进展,药物治疗有改善部分症状的作用。与此同时,中医药治疗痴呆具有巨大的潜力,总结和发掘中药的有效成分,建立统一的疗效观察指标和定量疗效评定的药理模型,在攻克痴呆中为人类提供新的希望。因此,进行中西医结合治疗痴呆是迫切需要研究的课题,我们探讨了中西医结合治疗老年性痴呆的临床疗效。中医药是我国的瑰宝,在目前老年期痴呆的治疗尚未有特异疗效的情况下,相比之下,中医药在延缓衰老以及衰老相关疾病的防治方面有着丰富的理论和实践经验,具有潜在的优势和广阔的开发前景。研究发现雌激素对女性认知功能有保护作用,设计了雌激素对女性阿尔茨海默病患者的对照观察的研究,提出了雌激素配合胆碱酯酶抑制剂治疗女性阿尔茨海默病患者的可能性,也取得了理想的效果,达到了改善老年期痴呆认知功能的预期目的,为女性阿尔茨海默病患者的治疗带了了福音。本文通过对痴呆的中西医结合治疗与康复观察研究,发现其有较好的疗效。总之寻找确切有效的防治方法,改善和提高患者的生存质量和对社会的适应能力,以最大程度减少痴呆类疾病所带来的不良后果,都有十分重要的意义。本文在认真研究国内外近期对痴呆的发病机制与治疗研究的基础上,以中西医结合施治与康复为主导思想,运用中医的特点,结合西医的作用,配合康复治疗,对痴呆,尤其是阿尔茨海默病和血管性痴呆进行预防、控制与治疗,取得了明显的疗效。首先提出并开展了中药提纯针剂(络泰)治疗老年期痴呆(本文主要指血管性痴呆和阿尔茨海默病痴呆)的疗效研究。不管血管性痴呆还是老年性痴呆(阿尔茨海默病),脑血流量的减少可能是共同的病理改变,而络泰的有效成分人参皂苷R1,且其是无菌冻干粉剂,有较高的稳定性。本课题的动物实验表明人参总皂甙对大鼠脑缺血再灌注损伤有明显的保护作用,表现在它可扩张血管,增加脑血流量,减轻脑水肿超微结构损伤和降低死亡率。其保护作用与抑制钙积累密切相关。临床应用证明它具有<WP=4>扩张心脑血管,增加心脑血管流量,改善心脑微循环,并对脑缺血后海马CAI区(与学习和记忆有关)的迟发性神经元损伤有明显的保护作用,且又抗炎作用和雌激素样作用, 临床实践证明,人参皂苷具有与雌激素相似的改善记忆和神经保护作用。雌激素参与中枢神经系统功能的调节,内源性雌激素是Alzheimer Disease(AD), 的保护因素,雌激素替代治疗对AD的预防和治疗有益。因此,人参皂苷作为具有雌激素样作用的中药,可以作为雌激素的替代品,对于AD的防治具有重 要意义。在动物衰老过程中,钙代谢平衡失调造成神经元中游离钙超负荷,使神经元可塑性减低,从而发生记忆障碍。李麟仙研究表明,同样人参皂苷的益智作用机制之一即它的有效成分中的Rb1能够降低细胞内钙的浓度及钙蛋白的活性。缩小脑梗死范围,从而有抗AD和Vascular Dementia(VD)作用。其次,研究了中草药治疗血管性痴呆的效果,方药组成为:黄芪、红花、枸杞子、五味子、赤芍、川芎、红花、当归、地龙。方中黄芪、红花、枸杞子、五味子可益气补肾,填精生髓;赤芍、川芎、红花、当归活血化瘀,地龙疏通经络。现代药理研究证明,黄芪、五味子、枸杞子对神经系统有兴奋作用,能改善人的智能活动;当归、川芎、赤芍、红花、五味子、黄柏均有不同程度的钙通道阻滞作用,可明显增加脑血流量,改善脑循环,清除自由基。地龙,赤芍含有纤维蛋白溶解酶激活物,有溶栓作用,绞股蓝抗衰老。所以以上诸药配伍可以提高患者血中超氧化物歧化酶的活性,降低过氧化脂质,抗自由基损伤,改善脑微循环,促进神经细胞功能恢复,并对脑缺血后海马CAI区(与学习和记忆有关)的迟发性神经元损伤有明显的保护作用,进一步延缓了痴呆的发生,为众多的血管性痴呆患者提供了价廉的治疗渠道。第三,提出并开展了从中草药千层塔中的提取物—石杉碱甲(胆碱酯酶抑制剂)配合雌激素治疗阿尔茨海默病的可行性,这和美国Research Nurse Coordinator Alzheimer’s Disease Research Center(Houston Baylor College of Medicine)目前几个重点研究阿尔茨海默病的研究机构,观察雌激素治疗阿尔茨海默病的研究几乎同步进行。流行病学证明,女性阿尔茨海默病的发病率远远高于男性,其可能的原因之一是因为雌激素水平的下降有关。雌激素对认知等有保护作用已达共识,本课题的研究表明:雌激素配合石杉碱甲治疗阿尔茨海默病对其认知功能等有保护作用,并且可加强石杉碱甲的疗效,为女性阿尔茨海默病的预防及治疗带来了希望。同时还小样本的采用了安理申配合雌激素治疗阿尔茨海默病的试验,取得了和国外同类研究的一致性。康复研究在老年期痴呆的治疗中起着举足轻重的作用。由于痴呆是一种慢性疾病<WP=5>且社会生活功能缺损日益加重,需要对其进行照料,而我国的国情决定了多数患者是在家庭内被照料,照料负担极?更多还原

【Abstract】 Dementia is a disease of acquired intelligence injury syndrome, caused by brain dysfunction. The incidence rate of Senile Dementia has been inclining to climb up, along with aging population. This has been an outstanding problem of society and medical science. Dementia therapy is a key point of improving the life quality of the aged. Dementia is a parenchymal disease, mostly irreversible. No satisfying therapy has been developed and those aimed to entity is still under research. Some promising progresses have been made in tentative drug treatment to several kinds of causations, some of whose symptoms are ameliorated. At the same time, traditional Chinese medicine (TCM) possesses great potential to fight against Dementia. Hopes lay in summarizing and uncovering effective components, and the creation of unitive pharmacody model, including observing guidelines and quantitative evaluation of effects. Therefore, applying the combination of TCM and west medicine to Dementia therapy is an urgent topic and we discussed its clinical effects. In comparison to west medicine, TCM, the gem of our country, has accumulated rich theories and practical experiences in postponing senility, and prevention and cure of the related diseases. Thus, TCM has great potential and bright prospect to be developed. Investigations revealed that estrin protects female cognitive function. We designed contrast researches to observe how estrin affects female patients with Alzheimer’s Disease (AD), suggested the possibility of cholinesterase inhibitor copulated with estrin for cure, and reached the objective of ameliorating cognitive function of Senile Dementia sufferers. This article found promising effects of the combination of TCM and west medicine to Dementia therapy by observing research of treatment and rehabilitation. In short, finding operative ways of prevention and cure, ameliorating and improving the patients’ life quality and ability to adapting the society, and lessening dysresults of Dementia, do possess great significance.First of all, we researched the effects of using LuoTai(络泰)to treat Senile Dementia which means Vascular Dementia and Alzheimer’s Disease here. Vascular Dementia and Senile Dementia (AD) probably share the same symptom of brain blood flow decrease. The effective component of LuoTai is ginsenoside R1, which is sterile dongganfenji, characterized with high stability. Experiments showed that ginsenoside can obviously protect rat brain from ischemia reperfusion injury, by dilating blood vessel, enhancing <WP=7>blood flow, ameliorating ultrastructure injury of brain edema, and decreasing death rate. This protective function is closely related to the accumulation of calcium. Clinical application proved its ability of dilating blood vessels, enhancing blood flow, ameliorating microcirculation, evidently preventing late neur injury of hippocamp’s CAI domain(related to study and memory) after brain ischemia, and resisting inflammation thus resisting AD and VD.Clinical practic also certified that ginseng is an effective TCM to prevent and cure AD Its active component ginsenoside has similar effects as estrin to ameliorate memory and protect nerve. Estrin takes part in central nervous system control, and intrinsic estrin is a protective factor of AD, and its replacement therapy is beneficial to the prevention and cure of AD. So, as a kind of TCM that having the same function of estrin, ginsenoside can be applied as a replacement of estrin and is important to prevent and cure of AD. During the course of animal aging, disturbance of calcium metabolism causes overload of free calcium in neuron, reduces neuron’s compliance, and then obstructs memory. Li Linxian ‘s research made clear that one of the mechanisms of improving intelligence is in virtue of the effective component Rb1’s ability to reduce [Ca2+]i and calcium protein activity, and cerebral infarction domain decrease.Next, we researched the effects of using TCM to treat Vascular Dementia. The researched prescription is: mongolian milkvetch root, safflower, barb更多还原