蒙醫(yī)放血療法對高脂血癥模型大鼠的作用機制研究
本文選題:蒙醫(yī)放血療法 + 高脂血癥模型大鼠; 參考:《北京中醫(yī)藥大學》2015年博士論文
【摘要】:高脂血癥即血清總膽固醇、甘油三酯、低密度脂蛋白增高,高密度脂蛋白降低,脂代謝紊亂是誘發(fā)心腦血管疾病的主要隱患,嚴重危害著人類健康。心腦血管病被WHO確認是危害人類健康的“頭號殺手",全世界每年大約有1500萬人死于心腦血管疾病.而美國動脈粥樣硬化性血管疾病的發(fā)病率高,是重要的致死性病因,每年約占所有死亡原因的1/3。美國成年人高脂血癥發(fā)病率大約占50%。在中國心腦血管疾病病死率,從上世紀60年代居第七位,現(xiàn)在己上升到第一位,有高脂血癥傾向者,約占人口的35%。尤其是血團總膽固醇水平升高是動脈粥樣硬化(AS)的重要危險因素之一。一旦引發(fā)則易增加心腦血管疾病的發(fā)病率和死亡率,從目前發(fā)生率有年輕化趨勢。預防和治療高脂血癥是近年來醫(yī)學研究的熱點。眾多的臨床研究表明放血療法對高脂血癥的治療存在優(yōu)勢。本課題采用放血療法治療高脂血癥模型大鼠,觀察脂質(zhì)代謝、抗氧化與內(nèi)皮功能及肝組織相關指標的影響,探討放血療法治療高脂血癥的機制,對蒙醫(yī)放血療法治療高脂血癥的臨床研究提供實驗依據(jù)。該論文文獻綜述部分和實驗部分兩個部分組成。文獻綜述部分主要敘述了高脂血癥的西醫(yī)發(fā)病機理、蒙醫(yī)病因分析和該病的治療現(xiàn)狀以及放血療法臨床應用方面。實驗部分:目的:通過放血療法治療高脂血癥模型大鼠實驗研究,初步探討蒙醫(yī)放血療法對高脂血癥的作用機制,預防和治療高脂血癥及其相關疾病提供實驗依據(jù)。方法:將50只wistar大鼠,體重(200士20)g以普通飼料進行適應性飼養(yǎng)1周,按體重隨機分為5組,每組10只,分別為空白對照組(A組)、氋脂血癥模型組(B組)、放血組(C組)、常規(guī)針刺組(D組)、陽性藥物對照組(E組);空白對照組以普通飼料喂養(yǎng),其他各組均以高脂飼料飼養(yǎng)。從第6周末開始,空白對照組和氋脂血癥模型組大鼠斷尾采血1次,檢測甘油三酯(TG)、總膽固醇(TC)、高密度脂蛋白膽固醇(HDL-C)、低密度脂蛋白膽固醇aDL"C),并計算動脈粥樣硬化指數(shù)(AI)進行對比,確定造模是否成功。第7周造模成功后,空白對照組以普通飼料喂養(yǎng),模型組和放血組、針刺組、陽性藥物對照組以高脂飼料繼續(xù)喂養(yǎng),其中放血組開始放血治療(放血前三籽湯1.8g\kg.d灌胃給藥三天,每日一次;第一次在右側(cè)臟腑總脈處放0.5ml血,第二次在左側(cè)肝腑總脈處放0.5ml血),一周一次,共兩周;針刺組每天足三里穴針剌20分鐘,每天一次,兩周為一療程;陽性藥物對照組每天脂必妥灌胃給藥(0.42g\kg.d),空白對照組每天灌胃0.3%CMC-鈉溶液。治療結(jié)束后取材檢測血清TG、TC、HDL-C、LDL-C,全血高切、低切、細胞壓積、紅細胞聚集指數(shù)、血i}粘度、紅細胞電泳時間等指標,血清中及肝臟組織中SOD的活力、MDA的含量、GSH-Px含量、血裝ET活性、血清NO、血架TXB2、6-keto-PGFl a、LPL、HL等指標;光鏡下觀察肝臟形態(tài)結(jié)構。結(jié)果:1.治療結(jié)束后血脂指標方面:TG、TC、LDL-C水平:C組與模型組比較P0.01,D、E組與模型組比較P0.05,說明C、D、E組均能降低TG、TC、LDL-C水平,但C組優(yōu)于D、E組;HDL-C水平:C、D、E組與模型組比較P0.05,說明C、D、E組均有升高HDL-C作用,但組間無明顯差異。2.血液流變學方面:C組與模型組比較全血高切、低切、細胞壓積、紅細胞聚集指數(shù)、血架粘度、紅細胞電泳時間均P0.01,極顯著;D、E組與模型組全血高切、低切、細胞壓積、紅細胞聚集指數(shù)、血菜粘度、紅細胞電泳時間比較均P0.05,有顯著性差異。說明調(diào)節(jié)血液流變學方面放血組優(yōu)于常規(guī)針刺組和脂必妥組。3.抗氧化指標方面:治療后SOD、GSH-Px: C、D、E組與模型組比較均P0.05,有顯著性差異,說明C、D、E組均有提氋SOD和GSH-Px作用;MDA:C、D、E組與模型組比較均P0.05,無顯著性差異,但MDA含量標準值比模型組低,說明降低MDA的趨向。4.血管內(nèi)皮功能方面:ET:與模型組比較D、E組均P0. 05,C組P0.01有顯著性差異,說明降低ET活性方面C組優(yōu)于D、E組。血清NO:與模型組比較C、D組均P0.05,E組P0.01有顯著性差異,說明提高NO方面E組優(yōu)于C、D組。5.血脂酶方面:LPL、HL含量:C、D、E組與模型組比較均P 0.05,說明C、D、E組能夠升高LPL、HL含量,但組間無顯著性差異。血菜中TXB2、6-Keto-PGFla影響:C、D、E組與模型組比較P0.05,無顯著性差異,說明三組治療方法對血i}中TXB2、6-Keto-PGFla的影響不明顯,但從標準值上看有降低血漿中TXB2、6-Keto-PGFla的趨勢。6.肝臟形態(tài)學方面:與模型組C、D、E組P0.05,有顯著性差異,說明C、D、E組對肝臟均有保護作用。結(jié)論:1.蒙醫(yī)放血療法能夠明顯降低高脂血癥血清TC、TG、LDL-C的水平,提高HDL-C水平。說明脂質(zhì)代謝方面具有良性調(diào)節(jié)作用。2.蒙醫(yī)放血療法能夠有效影響血液流變學相關指標,加快血流速度,防治動脈硬化及心腦血管疾病的發(fā)生。3.通過檢測高脂血癥血清和肝組織SOD、MDA、GSH-Px等指標,總結(jié)出蒙醫(yī)放血療法可增加抗氧化酶活性,減輕脂質(zhì)過氧化。4.放血療法對血裝ET血清NO的影響,可證明放血療法通過減輕血管內(nèi)皮的損害,可以阻止高脂血癥向AS及CHD的發(fā)展,這對預防和減低AS及CHD的發(fā)生具有重要意義。5.LPL是水解脂蛋白中的TG的重要酶類,HL主要在LDL-C和HDL-C代謝中起重要作用,放血療法通過升高LPL、HL含量,能夠調(diào)節(jié)血脂蛋白酶,從而達到調(diào)節(jié)脂質(zhì)代謝作用。6.蒙醫(yī)放血療法對肝臟形態(tài)學的變化說明放血療法可以改善肝臟脂肪細胞的代謝功能,保護肝臟的作用。
[Abstract]:Hyperlipidemia, such as serum total cholesterol, triglycerides, low density lipoprotein, high density lipoprotein, and lipid metabolism disorder, is the main hidden danger of cardiovascular and cerebrovascular diseases, which seriously endangers human health. Cardio cerebral vascular disease is confirmed by WHO as the "No. 1 killer", which is the first killer of human health, and about 15 million people die from heart and brain every year in the world. The incidence of atherosclerotic vascular disease in the United States is high, and it is an important cause of death. The incidence of hyperlipidemia in 1/3. American adults, which accounts for about all causes of death every year, accounts for about 50%. in the death rate of cardiovascular and cerebrovascular diseases in China. It was the seventh in the 60s of last century, and now it has risen to the first, with hyperlipidemia. It is one of the most important risk factors of atherosclerosis (AS) that the population of 35%., especially the increase of total cholesterol in the blood group, is one of the most important risk factors for atherosclerosis (AS). The study shows that blood letting therapy has advantages in the treatment of hyperlipidemia. This subject uses blood letting therapy to treat hyperlipidemia model rats, observe the effect of lipid metabolism, anti oxidation and endothelial function and liver tissue, explore the mechanism of hyperlipidemia treatment with blood letting therapy, and study the clinical study on hyperlipidemia treated by Mongolian medicine bleeding therapy. This paper provides an experimental basis. The literature review and experimental part are made up of two parts. The literature review mainly describes the pathogenesis of hyperlipidemia in western medicine, the analysis of the etiology of Mongolian medicine and the status of the treatment of the disease and the clinical application of the blood letting therapy. A preliminary study on the mechanism of hyperlipidemia, prevention and treatment of hyperlipidemia and its related diseases by Mongolian medicine bleed therapy. Methods: 50 Wistar rats, body weight (200, 20) g were adapted for 1 weeks with normal diet, and they were randomly divided into 5 groups according to body weight, 10 in each group (group A), respectively. The disease model group (group B), the blood group (group C), the routine acupuncture group (group D) and the positive drug control group (group E); the blank control group was fed with ordinary feed and the other groups were fed with high fat feed. From the sixth weekend, the blank control group and the rat model group were collected for 1 times, the triglyceride (TG), the total cholesterol (TC) and the high density lipoprotein were detected. Cholesterol (HDL-C), low density lipoprotein cholesterol aDL "C" and calculated the atherosclerotic index (AI) compared to determine whether the model was successful. After seventh weeks of success, the blank control group was fed with ordinary diet, the model group and the blood group, the acupuncture group, the positive drug control group continued to feed with high fat diet, of which the blood group began to release blood. The treatment (three seed soup before bleeding) was given to the three seed soup for three days, once a day; the first time to put 0.5ml blood in the right viscera general vein, and the second time to put 0.5ml blood in the total vein of the left liver Zang Fu, once a week for two weeks; the acupuncture group was punctured for 20 minutes every day at Zusanli, once a day and two weeks as a course of treatment; the positive drug control group was given the medicine every day. ( 0.42gkg.d), the blank control group was filled with 0.3%CMC- sodium solution every day. After the treatment, the blood serum TG, TC, HDL-C, LDL-C, whole blood high cutting, low cutting, hematocrit, erythrocyte aggregation index, blood i} viscosity, erythrocyte electrophoresis time and other indexes, the activity of SOD in serum and liver tissue, MDA content, GSH-Px content, ET blood activity, serum NO, blood TXB2,6-keto-PGFl a, LPL, HL and so on; observe the morphological structure of the liver under light microscope. Results: 1. after the end of the treatment, the blood lipid index: TG, TC, LDL-C level: C group and model group are compared with P0.01, D, E group and model group. The results showed that C, D and E groups increased the effect of HDL-C, but there was no significant difference in.2. blood rheology between groups: C group and model group compared full blood, low cut, cell pressure, erythrocyte aggregation index, blood frame viscosity, erythrocyte electrophoresis time P0.01, very significant; D, E group and model group all blood high cut, low cut, cell pressure product, erythrocyte aggregation index, blood vegetable sticky Degree, erythrocyte electrophoresis time compared with P0.05, there are significant differences. It shows that the regulation of Hemorheology in the blood group is better than the conventional acupuncture group and the.3. antioxidant index in the lipbally group: after the treatment, SOD, GSH-Px: C, D, E group are all P0.05, and there are significant differences between the group and the model group. The model group was all P0.05, but there was no significant difference, but the standard value of MDA content was lower than that of the model group. It showed that the tendency of reducing MDA was.4. vascular endothelial function: ET: was compared with model group D, E group was P0. 05, C group P0.01 had significant difference, which showed that C group in the aspect of reducing ET activity was better than that of model group. There was no significant difference between the group E and the model group. There was no significant difference between the group and the model group. There were no significant differences between the group and the model group. There was no significant difference between the group and the model group, which showed that there were three groups of treatment methods for blood NO. } the effect of TXB2,6-Keto-PGFla is not obvious, but from the standard value, there is a tendency to reduce the trend of TXB2,6-Keto-PGFla in the plasma.6. liver morphology: with the model group C, D, E group P0.05, there are significant differences, indicating that C, D, E group have protective effects on the liver. Conclusion: 1. Mongolian medicine therapy can obviously reduce the serum TC, TG, and water of hyperlipidemia. Level, improve the level of HDL-C. It shows that lipid metabolism has a benign regulation effect,.2. Mongolian medicine blood letting therapy can effectively affect blood rheology related indexes, speed up blood flow speed, prevent arteriosclerosis and cardio cerebral vascular diseases,.3. through detecting SOD, MDA, GSH-Px and other indexes of hyperlipidemia serum and liver tissue, sum up the Mongolian medicine bleeding therapy. The method can increase the activity of antioxidant enzymes and reduce the effect of lipid peroxidation.4. bleeding therapy on the serum NO of blood loaded ET. It is proved that blood letting therapy can prevent the development of hyperlipidemia to AS and CHD by reducing the damage of vascular endothelium, which is important to prevent and reduce the occurrence of AS and CHD.5.LPL is an important enzyme of TG in the hydrolytic lipoprotein. HL plays an important role in the metabolism of LDL-C and HDL-C. Blood letting therapy can regulate lipid protease by increasing LPL, HL content and regulating blood lipid protease, thus it can regulate the changes of liver morphology by regulating the lipid metabolism effect of.6. Mongolian medicine. It shows that blood therapy can improve the metabolic function of liver fat cells and protect the liver.
【學位授予單位】:北京中醫(yī)藥大學
【學位級別】:博士
【學位授予年份】:2015
【分類號】:R29;R-332
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