神经退行性病变机制及其药物干预对策  

Pathologic Mechanism of Neurodegenerative Disorders and Drug Intervention

作　　者：纳涛[1] 戴德哉[1] 

机构地区：[1]中国药科大学药理研究室,江苏南京210009

出　　处：《药学进展》2005年第3期97-101,共5页Progress in Pharmaceutical Sciences

基　　金：国家自然科学基金重点项目资助 (30 2 30 170 ) ;国家自然科学基金面上项目资助 (30 1710 78)

摘　　要：综述神经退行性病变的特点和表现及其相关内源性物质 ,探讨该类病变机制及其药物干预对策。神经退行性病变可由多种因素造成 :脑内 β 淀粉样蛋白沉着导致阿尔茨海默病 ;皮层下区域病变导致帕金森病和Hunt ington病 ;另外 ,非特异性老年性脑内神经元病可变使神经元减少 ,导致老年性智力衰退 ;血管内皮细胞损害与脑神经元及脑功能有相关性 ;老年性血管内皮细胞中一氧化氮 (NO)生物利用度下降以及脑内某些脑区内一氧化氮合酶活性及NO异常上调与脑内神经元变性相关 ;老年人脑供血不足是由于舒血管物质减少而缩血管物质增多 ,使血管收缩及舒张功能改变所致 ,是造成脑内神经元逐年递减的一个重要因素。老年人的血管活性障碍与糖尿病病人有相似之处 ,亦是由于体内非酶糖基化产物的生成 ,使内皮细胞功能损害、内皮素 (ET1)及ONOO· -增多 ,最终导致氧化应激。以保护血管内皮细胞为主要靶点的药物治疗 ,可通过抗氧化应激、降低ET1水平、改善血管重构及多靶点作用 ,并结合节制饮食、加强锻炼等非药物治疗 ,可改善神经退行性病变 ,提高老年人的智力功能和生活质量。The characteristics and manifestations of neurodegenerative disorders and the relative endogenous materials were summarized and their pathologic mechanisms and drug intervention were discussed. Neurodegenerative disorders may result from many factors, i.e. β-amyloid deposition causes Alzheimer's disease, the lesion of subcortical region induces Parkinson's disease and Huntington disease, the non-specific loss of neuron in senile brain starts the senile intelligence decline. It is thought that there is a possible relationship between the degeneration of vascular endothelial cells and the functions of cranial neurons and brain. Declined bioavailability of NO in senile vascular endothelial cells and the abnormally up-regulation of NOS activity and NO level in certain areas of brain are associated with cranial neuron denaturalization and insufficient blood supply in the senile brain, which is caused by the dysfunction of vascular contraction and dilatation, is also an important reason of neuron degeneration. Similarly in diabetic patients, vascular degeneration in senile can be raised by the production of AGEs (advanced glycosylation end products). AGEs damage the function of vascular endothelial cell, increase the production of ET-1 (endothelin-1) and ONOO ·- and finally result in oxidative stress. Drug intervention targeting a protection of endothelial cells of blood vessel, such as inbibiting oxidative stress, lowering ET 1 level, reversing remodeling and multi-tartgeting action, and combining with non-drug therapy such as dietary restriction and exercise, can ameliorate neurodegenerative disorders effectively and improve the elder's intelligence and living quality.

关 键 词：神经退行性病变 阿尔茨海默病 内皮细胞 氧化应激 内皮素 药物干预 

分 类 号：R741[医药卫生—神经病学与精神病学]