丹参干预阿尔茨海默病模型大鼠免疫炎性损伤的实验研究

【作者】 董文会；

【导师】 吕爱平；

【作者基本信息】 辽宁中医药大学 ， 中医基础理论， 2009， 硕士

【摘要】 阿尔茨海默病(Alzheimers disense AD)又称老年性痴呆,是由于脑功能障碍而产生的获得性智能损害综合症,是与年龄相关的记忆丧失和高级认知功能减退的神经系统退行性疾病。中医认为本病的发生以五脏虚损为本,瘀血、痰浊停留体内为标。本实验研究以活血化瘀药丹参作为本病治疗的切入点,探讨丹参对阿尔茨海默病的治疗机制。目的:本实验研究重在探讨丹参在干预阿尔茨海默病Aβ模型大鼠免疫炎性损伤中的作用,主要观察丹参对模型大鼠炎性细胞因子白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的影响,探讨丹参的作用机制,为中药治疗阿尔茨海默病提供科学依据。材料与方法:采用Aβ淀粉样蛋白注射大鼠海马方法塑造阿尔茨海默病模型,分别给以中药丹参、西药吲哚美辛、生理盐水灌胃,四周后,水迷宫实验观察药物对模型大鼠学习记忆能力的影响;采用ELISA双抗体夹心法,检测不同组别大鼠血清中细胞因子IL-6、TNF-α的表达变化。结果:在水迷宫实验中,给予中药和西药的大鼠与给药前的大鼠比较,其逃避潜伏期有所缩短,说明两种药物对AD大鼠的学习记忆能力有改善作用。在细胞因子检测方面,模型组与假手术组比较,模型组的IL-6、TNF-α均有较高水平的表达,说明注射Aβ淀粉样蛋白使大鼠血清中IL-6、TNF-α的分泌明显增加,而丹参组、西药组与模型组比较,IL-6、TNF-α的分泌降低,提示丹参和西药均能对AD大鼠血清中IL-6、TNF-α的表达有很好的抑制作用。结论:1采用Aβ淀粉样蛋白注射大鼠海马方法塑造的阿尔茨海默病的模型大鼠,逃避潜伏期延长,学习记忆能力下降。大鼠血清中IL-6、TNF-α等细胞因子表达增高,可能是阿尔茨海默病模型大鼠的病理变化之一。2丹参可以提高模型大鼠的学习记忆能力,抑制AD大鼠血清中IL-6、TNF-α等细胞因子的表达,提示丹参抑制AD模型大鼠的免疫炎性损伤,可能是其防治阿尔茨海默病的机制之一。更多还原

【Abstract】 Alzheimers disease(AD),also named as senile dementia,is an acquired syndrome of intelligence injury because of cerebral disfunctions,It is a retrograde disease of nerve system related to loss of memory and hypofunction of higher cognition.TCM thinks the origin is consumptive disease of five viscera and the superficiality is the stagnation of blood and phlegm in the body.Basing on of Danshen’ function of promoting blood circulation by removing blood stasis,in this experiment study we investigate mechanism of Danshen in treatment of AD.Purpose:To study the function of Danshen to immune inflammation injury of Aβmodel AD Wister rats,to observe the effect of Danshen to inflammatory bell genesIL-6,TNF-αof model Wister rats,and to discuss the effective mechanism of Danshen so as to provide scientific evidence for TCM to treate AD.Material and method:The rat AD models were set up by Aβ-amyloid protein injection into the Hippocampus Wister rats,for them traditional Chinese medicine Danshen,Western medicine indomethacin,and saline were administered. After four weeks,effect of drugs on learning and memory in rats is observed by the water maze experiment:ELISA method was used to detect expressions of cytokines serum IL-6,TNF-αin all groups.Results:In the water maze experiment,compared with pre-administration rats, the incubation and escape times of Wister rats given Chinese medicine and Western medicine had been shortened,lt showed that the two drugs for AβWister rats can improve learning and memory ability.In cytokines detection,compared with sham operation group,the IL-6,TNF-αin model group had higher level of expression.It showed that injection of Aβamyloid protein could make secretions of IL-6,TNF-αin serum significantly increase.Compared with model group, IL-6,TNF-αsecretion in the Chinese medicine group and western medicine group reduced.It revealed that both Chinese medicine and western medicine could inhibit expression of IL-6,TNF-αin the AβWister rats serum.Conclusion:1 The escaping latency of AD model Wister rats established by using Aβ-amyloid protein injection in to the Hippocampus is prolonged,learning and memory decline expression of cytokines increased in serum IL-6,TNF-αis increased,which may be one of the pathological changes in Wister rat AD models.2 Danshen can improve learning and memory of rat models and inhibit the expression of cytokines IL-6,TNF-αin AD serum.It shows of inhibition to the immune inflammatory injury of AD model Wister rats may be one of the mechanisms更多还原