血栓心脉宁对血管性痴呆大鼠的治疗作用及机制初探

发布时间：2018-12-14 03:49

【摘要】：血管性痴呆(Vascular Dementia，VD)是由脑卒中或长期慢性脑缺血等各种脑血管疾病引起的广泛或局灶的脑功能障碍导致的痴呆综合症。患者多表现为记忆减退、认知功能障碍。随着人口老龄化的加剧，VD的发病率逐年上升，给个人、家庭及社会带来了沉重负担。目前治疗VD的药物主要包括胆碱酯酶抑制剂、脑循环改善药及神经元保护药等药物，这些药物中有的具有一些不良反应，有的经济成本较高，使应用受到限制，，因而找寻疗效高、毒性小的药物是药学工作者重要的研究方向。血栓心脉宁是由丹参、川芎、毛冬青、水蛭、槐花、麝香、冰片、牛黄、人参茎叶皂苷、蟾酥等十几味名贵中药材采用现代加工工艺炮制而成的。临床上广泛应用于脑梗塞、冠心病、心绞痛等心脑血管疾病的治疗。大量的研究表明血栓心脉宁具有抗自由基氧化损伤、降低MDA含量，改善循环，抑制血栓形成等作用，这些作用与血管性痴呆的发病机制密切相关。血栓心脉宁对血管性痴呆是否有治疗作用，国内外文献尚未见报道。本研究采用双侧颈总动脉阻断致大鼠血管性痴呆模型，连续灌胃给药8w（血栓心脉宁小剂量组1.10g/kg、血栓心脉宁大剂量组2.20g/kg），通过行为学（水迷宫、避暗）、胆碱酯酶、自由基及相关酶（MDA、SOD、CAT、GSH-Px、Na+-K+-ATPase、Ca2+-Mg2+-ATPase）和病理检查，观察了血栓心脉宁对VD大鼠的治疗作用，并对其作用机制进行了初步探讨。行为学实验水迷宫实验结果显示，与模型组相比，血栓心脉宁小剂量组（1.10g/kg）在第2天、第5天的潜伏期及游程缩短（P0.01或P0.05），第1～6天到达平台的朝向角、游泳速度均无显著改变。血栓心脉宁大剂量组（2.20g/kg）在第2～6天潜伏期缩短（P0.05），第1～6天的游程缩短（P0.05），第1～6天到达平台的游泳速度无明显变化，第3天和第4天到达平台的朝向角明显变小（P0.05）。第7天血栓心脉宁小、大剂量组VD大鼠在2min内经过平台的次数、经过有效区的次数、平台停留时间、平台停留距离、有效区停留时间、有效区停留距离、平台停留时间占总时间的百分比、平台停留距离占总路程的百分比、有效区停留时间占总时间的百分比和有效区停留距离占总路程的百分比均无显著变化。避暗实验结果显示，与模型组比较，血栓心脉宁小、大剂量组VD大鼠在第2天避暗错误潜伏期及错误次数，均无显著性差异。血栓心脉宁小剂量组（1.10g/kg）大鼠脑组织胆碱酯酶无明显变化；血栓心脉宁大剂量组（2.20g/kg）大鼠脑组织胆碱酯酶有降低趋势，但无统计学意义。自由基及相关酶检测结果显示，与模型组比较，血栓心脉宁小剂量组（1.10g/kg）大鼠脑组织MDA及SOD无明显变化；血栓心脉宁大剂量组（2.20g/kg）MDA含量降低（P0.05），SOD活性升高（P0.05）。与模型组比较，血栓心脉宁小、大剂量组大鼠脑组织GSH-Px、CAT、Na+-K+-ATPase、Ca2+-Mg2+-ATPase无明显变化。病理检查血栓心脉宁小、大剂量组均可以减轻VD大鼠大脑皮层及海马的病理变化。本研究结果显示血栓心脉宁对VD大鼠有治疗作用，其作用机制可能与提高抗自由基相关酶，减轻自由基损伤有关。
[Abstract]:Vascular Dementia (VD) is a dementia syndrome caused by a wide or range of brain dysfunction caused by various cerebrovascular diseases such as stroke or long-term chronic cerebral ischemia. The patients showed hypomnesis and cognitive dysfunction. With the aging of the population, the incidence of VD has increased year by year, which has brought a heavy burden on the individual, family and society. The medicine for treating VD mainly comprises a drug such as a cholinesterase inhibitor, a brain circulation improving agent and a neuron protecting medicine, The medicine with small toxicity is the important research direction of the pharmaceutical worker. The preparation method comprises the following steps of: processing a plurality of rare traditional Chinese medicinal materials, such as red sage root, Sichuan root, pubescent holly, leech, pagodatree flower, musk, borneol, bezoar, ginseng, stem and leaf, and venenum bufonis, It is widely used in the treatment of cardiovascular and cerebrovascular diseases such as cerebral infarction, coronary heart disease, and angina pectoris. A large number of studies have shown that the thromboxine has the effects of resisting free radical oxidative damage, reducing the content of MDA, improving the circulation, inhibiting thrombosis, and the like, and the effects are closely related to the pathogenesis of vascular dementia. On the treatment of vascular dementia, the literature has not been reported at home and abroad. In this study, the model of vascular dementia was induced by double-sided common carotid artery occlusion, and 8w (1. 10 g/ kg of the low-dose of the high-dose and 2. 20 g/ kg of the high-dose group in the high-dose group) was given by intragastric administration, and the behavior (water maze, avoidance of dark), cholinesterase, free radical and related enzymes (MDA, SOD, CAT, GSH-Px, Na +-K +-ATPase, Ca 2 +-Mg 2 +-ATPase, and pathological examination were performed to observe the therapeutic effect of thrombosis on VD rats. Step into the discussion. The experimental results of the experimental water maze show that the latency and run-time of the low-dose group (1. 10g/ kg) in the lower-dose group (1. 10g/ kg) on the second day, the fifth day, and the run-time shortened (P0.01 or P0.05) as compared with the model group, and the orientation angle and the swimming speed of the platform at the first to sixth day. There was no significant change in the degree of swimming. The latency of the high-dose group (2.20g/ kg) in the high-dose group (2.20g/ kg) was shortened at the 2nd to 6th day (P0.05). The run-time of the first to 6th day was shortened (P0.05). The swimming speed of the platform at the 1st to 6th day was not changed significantly. The angle of the arrival of the platform at the 3rd and 4th days was significantly smaller. (P0.05). On the 7th day, the patients with high-dose group VD were treated with the platform in 2min, the number of effective areas, the residence time of the platform, the distance between the platform, the residence time of the effective area, the distance of the effective area, and the residence time of the platform. the percentage of the total time, the percentage of the total distance occupied by the platform, the percentage of the total time occupied by the effective area and the percentage of the stay distance of the effective area as a percentage of the total distance, The results of the dark-dark experiment showed that, compared with the model group, the latency and the error of the dark-dark-error latency and the error in the second day were compared with that of the model group. There was no significant difference in the number of cholinesterase in the brain tissue of the low-dose group (1. 10 g/ kg), and the cholinesterase in the brain tissue of the high-dose group (2. 20 g/ kg) in the high-dose group (2. 20 g/ kg) decreased. The results of free-radical and related enzymes showed that the MDA and SOD in the brain of the low-dose group (1. 10 g/ kg) of the high-dose group (1. 10 g/ kg) did not change significantly with the model group, and the content of MDA in the high-dose group (2.20g/ kg) was lower (P0.05). The activity of OD was increased (P0.05). Compared with the model group, the activity of GSH-Px, CAT, Na +-K +-ATPase and Ca2 +-Mg2 + in the brain of the rats with small and high dose group were small. There was no significant change in the +-ATPase. D. The pathological changes of cerebral cortex and hippocampus of the rats. The results of this study show that the effect of thrombosis in the treatment of VD rats may be related to the improvement of the mechanism.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R749.13

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