【作者】 于振波；

【导师】 刘宏雁；

【作者基本信息】 吉林大学 ， 药理学， 2012， 硕士

【摘要】 痴呆是一种持续性的智能障碍。老年期痴呆主要有两种：一是老年性痴呆，即阿尔茨海默氏病；二是血管性痴呆。老人患病后常表现为认知能力、自理能力下降，并伴有不同程度的行为精神症状，严重危及老人的健康，给家庭、社会造成了巨大负担。临床上主要的治疗方法虽然可以减轻症状，改善功能，但并不能阻止或逆转疾病的进程，且具有一定的不良反应。目前的研究显示中药在治疗痴呆方面有一定的优势，在中药中寻找治疗痴呆的有效药物是目前医药界主要的研究方向。文献报道，人参二醇可通过改变中枢神经递质和保护神经元作用（抗氧化、抗凋亡、保护线粒体、降低tau蛋白过度磷酸化及影响细胞信号传导），改善痴呆的症状。新人参二醇是人参二醇经酸、碱降解并纯化后得到的高纯度人参二醇，其通过增强部分基团结构，有可能使其某些药物活性增加。本论文实验通过行为学（水迷宫及避暗）、生化指标（胆碱系统，自由基）及病理检测，观察新人参二醇对老年大鼠痴呆的影响。1．新人参二醇对老年大鼠双侧颈总动脉结扎致血管性痴呆的影响双侧颈总动脉结扎致老年大鼠血管性痴呆，造模2个月后，按体重分为假手术组、模型组、阳性药安理申组（1.75mg/kg）及新人参二醇（20mg/kg）组灌胃给药15天，行为学检测期间继续给药，通过行为学（水迷宫）、生化指标（胆碱系统，自由基）及病理检测，观察新人参二醇对老年大鼠血管性痴呆（VaD）的影响。新人参二醇（20mg/kg），连续给药15天，行为学期间继续给药，与模型组比：水迷宫结果显示，新人参二醇（20mg/kg）组大鼠第1天至第6天到达平台的潜伏期、游程、朝向角、游泳速度及寻台策略无明显变化，第7天2min内大鼠在平台区的逗留时间、平台象限内的逗留时间、穿越平台次数、平台象限内游程占总游程百分比，朝向角和平均速度均无显著差异；胆碱能检测显示，新人参二醇（20mg/kg）组对AChE活性无影响；自由基检测结果显示，新人参二醇组（20mg/kg）大鼠脑组织MDA含量降低（P＜0.05），SOD活性升高（P＜0.05），CAT活性升高（P＜0.01）、SOD活性升高（P＜0.05），GSH-px活性有升高的趋势，但无统计学意义，Na⁺-K⁺-ATPase及Ca²⁺-Mg²⁺-ATPase活性均无明显差别。病理学结果显示，新人参二醇（20mg/kg）组大鼠海马CA1区锥体细胞和大脑皮质神经元的损伤程度较模型组有所减轻。结果提示：新人参二醇改善双侧颈总动脉结扎致老年大鼠血管性痴呆病理变化，减轻自由基的损伤。2．新人参二醇对Aβ致老年大鼠AD的影响大脑定位注射Aβ致老年大鼠老年性痴呆（AD）模型，造模3天后，按体重分为假手术组、模型组、阳性药安理申组（1.75mg/kg）及新人参二醇（10mg/kg，20mg/kg）组，灌胃给药15天，行为学检测期间继续给药，通过行为学（水迷宫，避暗）、生化指标（胆碱系统，自由基）及病理学检测，观察新人参二醇对老年大鼠老年性痴呆的影响。新人参二醇（10mg/kg、20mg/kg），连续给药15天，行为学期间继续给药，与模型组比：水迷宫结果显示：新人参二醇（10mg/kg、20mg/kg）组大鼠第1天至第6天到达平台的潜伏期，平台游程，朝向角，游泳速度，寻台策略无明显变化。第7天大鼠在2min内在平台区的逗留时间，平台象限内的逗留时间，穿越平台次数及平台象限内游程占总游程百分比，游泳平均速度及朝向角无差别；从避暗实验结果来看：新人参二醇（10mg/kg、20mg/kg）大鼠在第二天避暗的潜伏期和错误次数均无显著差异；从胆碱能检测来看，新人参二醇（10mg/kg、20mg/kg）对大脑定位注射Aβ致AD老年大鼠AChE无明显的影响；从自由基检测结果来看，新人参二醇（10mg/kg、20mg/kg）组大鼠脑组织中MDA含量降低（P＜0.01），SOD活性升高（P＜0.05），GSH-px活性升高（P＜0.01），CAT活性有升高（P＜0.05，P＜0.01），Na⁺-K⁺-ATPase活性升高（P＜0.01），Ca²⁺-Mg²⁺-ATPase活性无明显差别。病理学检查结果显示，新人参二醇（10mg/kg、20mg/kg）组的大鼠海马CA1区锥体细胞和大脑皮质神经元损伤程度较模型组明显减轻。结果提示：新人参二醇改善Aβ所致老年大鼠AD病理变化，减轻自由基的损伤。更多还原

【Abstract】 Dementia is a continual mental retardation. Alzheimer’s disease and vascular dementiaare the major styles of the senile dementia.The symptoms of the patients often containcognitive and self-care ability decreased, with varying degrees of behavioral andpsychological disorders. The diseases endanger the health of the elder, also led to anenormous burden to the family and society. The symptoms and functions of dementia canbe reduced through treament, but it does not stop or reverse the disease processing. Thepresent study shows that traditional Chinese medicine has some advantages in the treatmentof dementia, and to find effective drugs for the treatment of dementia in traditional Chinesemedicine becomes a main medicine research.In recent year, it is reported that panaxadiol may improve the symptoms of dementiaby altering the neurotransmitters and protecting neurons（antioxidant, anti-apoptotic,protection of mitochondria, reducing tau protein hyperphosphorylation and affecting cellsignaling）.The novel panaxadiol is high-purity panaxadiol, by panaxadiol degradation of acidand base and purification. The structural changes of some groups might influence somepharmacological activity.The aim of our study was to evaluate the effect of novel panaxadiol on VaD and ADin aged rats by behavior （water maze）test, biochemical indexs （the cholinergic system, freeradicals） and the pathological examination.1. the effect of novel panaxadiol on VaD in aged ratsAnimal model of VaD caused by bilateral carotid artery occlusion（2-VO）. Rats aredivided into control group, model group, acricept group and the novel panaxadiol （20mg/kg）group according to the body weight after2months.The novel panaxadiol （20mg/kg） group was intragastric administration for15days,and continued to administration during behavior tests，compared with the model group:①inthe water maze, novel panaxadiol （20mg/kg） group rats had no significant changes inlatency, swimming distance, starting angle, average velocity, and strategy to findingplatform from the1st day to the6th day; there was also no significant diffenerces in totletime in the platform, time cross the platform, totle time in the quadrant of platform, averagevelocity, starting angle, distance in the quadrant of platform/totle swimming distance on the 7th days in2min;②The new panaxadiol （20mg/kg） had no effect on AChE activity;③MDA level decreased （P <0.05）, SOD activity increased （P <0.05）, CAT activityincreased （P <0.05）, GSH-px activity had a trend to increased, Na⁺-K⁺-ATPase andCa²⁺-Mg²⁺-ATPase activity did not change in rat brain tissue.④The pathological resultsshowed the injuries of hippocampal CA1pyramidal cells and cortical neurons was reducedin the new panaxadiol （20mg/kg） groups rats.We came to a conclusion that the novelpanaxadiol may improve VaD by reducing damage of free radical.2. the effect of novel panoxadiol on AD in aged ratAnimal model of AD induced by microinjection of Aβ. Rats were divided into controlgroup, model group, acricept group and the novel panaxadiol （10mg/kg,20mg/kg） groupaccording to the body weight after3days.The novel panaxadiol （10mg/kg,20mg/kg） group were intragastric administration for15days, and continued to administration during behavior tests, compared with the modelgroup:①i n the water maze,novel panaxadiol （10mg/kg,20mg/kg） group rats had nosignificant changes in latency, swimming distance, starting angle, average velocity, andstrategy to finding platform from the1st day to the6th day; there is also no significantdiffenerces in totle time in the platform, time cross the platform, totle time in the quadrantof platform, average velocity, starting angle, distance in the quadrant of platform/totleswimming distance on the7th days in2min;②The passive avoidance results showed thatthe latency and the errors times were not significant differences on the2nd day in novelpanaxadiol（10mg/kg,20mg/kg） group rats;③The new panaxadiol （10mg/kg,20mg/kg）had no effect on AChE activity;④MDA level decreased （P <0.01）, SOD activityincreased（P <0.05）, GSH-px activity increased（P <0.05,P <0.01）, CAT activity increased（P<0.05,P <0.01）, Na⁺-K⁺-ATPase activity increased （P <0.01）and Ca²⁺-Mg²⁺-ATPaseactivity was no significant difference in brain tissue⑤The pathological results showed theinjuries of hippocampal CA1pyramidal cells and cortical neurons was significantlyreduced in the new panaxadiol （10mg/kg,20mg/kg） groups rats. The results suggest thatthe novel panaxadiol may improve AD by reducing the damage of free radical in aged rats.更多还原