血栓心脈寧對血管性癡呆大鼠的治療作用及機制初探
發(fā)布時間：2018-12-14 03:49
【摘要】：血管性癡呆(Vascular Dementia，VD)是由腦卒中或長期慢性腦缺血等各種腦血管疾病引起的廣泛或局灶的腦功能障礙導(dǎo)致的癡呆綜合癥。患者多表現(xiàn)為記憶減退、認知功能障礙。隨著人口老齡化的加劇，VD的發(fā)病率逐年上升，給個人、家庭及社會帶來了沉重負擔(dān)。目前治療VD的藥物主要包括膽堿酯酶抑制劑、腦循環(huán)改善藥及神經(jīng)元保護藥等藥物，這些藥物中有的具有一些不良反應(yīng)，有的經(jīng)濟成本較高，使應(yīng)用受到限制，，因而找尋療效高、毒性小的藥物是藥學(xué)工作者重要的研究方向。 血栓心脈寧是由丹參、川芎、毛冬青、水蛭、槐花、麝香、冰片、牛黃、人參莖葉皂苷、蟾酥等十幾味名貴中藥材采用現(xiàn)代加工工藝炮制而成的。臨床上廣泛應(yīng)用于腦梗塞、冠心病、心絞痛等心腦血管疾病的治療。大量的研究表明血栓心脈寧具有抗自由基氧化損傷、降低MDA含量，改善循環(huán)，抑制血栓形成等作用，這些作用與血管性癡呆的發(fā)病機制密切相關(guān)。血栓心脈寧對血管性癡呆是否有治療作用，國內(nèi)外文獻尚未見報道。 本研究采用雙側(cè)頸總動脈阻斷致大鼠血管性癡呆模型，連續(xù)灌胃給藥8w（血栓心脈寧小劑量組1.10g/kg、血栓心脈寧大劑量組2.20g/kg），通過行為學(xué)（水迷宮、避暗）、膽堿酯酶、自由基及相關(guān)酶（MDA、SOD、CAT、GSH-Px、Na+-K+-ATPase、Ca2+-Mg2+-ATPase）和病理檢查，觀察了血栓心脈寧對VD大鼠的治療作用，并對其作用機制進行了初步探討。 行為學(xué)實驗 水迷宮實驗結(jié)果顯示，與模型組相比，血栓心脈寧小劑量組（1.10g/kg）在第2天、第5天的潛伏期及游程縮短（P0.01或P0.05），第1～6天到達平臺的朝向角、游泳速度均無顯著改變。血栓心脈寧大劑量組（2.20g/kg）在第2～6天潛伏期縮短（P0.05），第1～6天的游程縮短（P0.05），第1～6天到達平臺的游泳速度無明顯變化，第3天和第4天到達平臺的朝向角明顯變�。≒0.05）。第7天血栓心脈寧小、大劑量組VD大鼠在2min內(nèi)經(jīng)過平臺的次數(shù)、經(jīng)過有效區(qū)的次數(shù)、平臺停留時間、平臺停留距離、有效區(qū)停留時間、有效區(qū)停留距離、平臺停留時間占總時間的百分比、平臺停留距離占總路程的百分比、有效區(qū)停留時間占總時間的百分比和有效區(qū)停留距離占總路程的百分比均無顯著變化。 避暗實驗結(jié)果顯示，與模型組比較，血栓心脈寧小、大劑量組VD大鼠在第2天避暗錯誤潛伏期及錯誤次數(shù)，均無顯著性差異。 血栓心脈寧小劑量組（1.10g/kg）大鼠腦組織膽堿酯酶無明顯變化；血栓心脈寧大劑量組（2.20g/kg）大鼠腦組織膽堿酯酶有降低趨勢，但無統(tǒng)計學(xué)意義。 自由基及相關(guān)酶檢測結(jié)果顯示，與模型組比較，血栓心脈寧小劑量組（1.10g/kg）大鼠腦組織MDA及SOD無明顯變化；血栓心脈寧大劑量組（2.20g/kg）MDA含量降低（P0.05），SOD活性升高（P0.05）。與模型組比較，血栓心脈寧小、大劑量組大鼠腦組織GSH-Px、CAT、Na+-K+-ATPase、Ca2+-Mg2+-ATPase無明顯變化。 病理檢查血栓心脈寧小、大劑量組均可以減輕VD大鼠大腦皮層及海馬的病理變化。 本研究結(jié)果顯示血栓心脈寧對VD大鼠有治療作用，其作用機制可能與提高抗自由基相關(guān)酶，減輕自由基損傷有關(guān)。
[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.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R749.13
本文編號：2377862
[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.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R749.13
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