清热燥湿法干预2型糖尿病及其大血管早期病变的动物研究

发布时间：2018-05-24 00:41

本文选题：2型糖尿病 + 大血管病变　；参考：《南京中医药大学》2017年硕士论文

【摘要】：研究背景:2型糖尿病(Type 2 diabetes mellitus,T2DM)是一种由多病因引起的以慢性高血糖为特点的代谢性疾病,其不仅发病率高,且患病率亦呈现升高趋势。2型糖尿病的并发症多种多样,大血管病变是其主要的并发症之一,包括主动脉、冠状动脉在内的大血管的动脉粥样硬化形成在2型糖尿病患者群中的发病率较正常人明显升高,是致死的重要原因之一。在早期调节血糖、血脂,预防或减轻大动脉病变是干预2型糖尿病及其大血管病变的主要目的。目的:通过实验观察清热燥湿法代表方--加减四妙散对于2型糖尿病动物模型的血糖、血脂及主动脉病变的干预作用,为临床应用提供依据。方法:实验分为两部分进行,第一部分实验为加减四妙散对于2型糖尿病小鼠血糖血脂的影响,通过采用腹腔注射链脲佐菌素(STZ)+高脂饲料喂养制造2型糖尿病模型,选取成模小鼠(空腹血糖FBG11.1mmol·L-1)随机分为:模型组、空白组、四妙低、中、高剂量组和阳性药(二甲双胍)组。采取灌胃给药,每天1次,持续3周后禁食12h后测血糖、血脂等相关指标。第二部分实验为加减四妙散对于动脉硬化大鼠早期病变的研究,取SPF级SD大鼠60只雌雄各半,随机分为6组:空白,阳性,模型,四妙低剂量,中剂量,高剂量组。除空白组外,余以18%猪油、7%胆固醇、1%牛胆盐、花生油配成糊状乳糜液按照1ml·100g-1每天灌胃一次,连续8周造模,8周后给药,同时维持造模,给药6周后禁食12h,处死取血液检测CHOL、TG,Glu,LDL-C、HDL-C、CGRP、抵抗素含量,取心脏及主动脉做病理切片,观察各组主动脉病理状况。结果:第一部分实验结果表明与空白组比较,治疗前模型组血糖和血脂含量与对照组比较均显著升高(P0.01)。与模型组比较,治疗后加减四妙散低、中、高剂量组血糖含量均显著下降(P0.05,P0.01),加味四妙散中、高剂量组血脂含量均显著下降(P0.01),低剂量组TG、HDL-C、LDL-C含量未见显著差异。第二部分实验结果说明与空白组相比,模型组血清中CHOL、TG、Glu含量均升高(P0.05,P0.01)LDL-C含量较对照组升高(P0.01);同时病理显示高脂模型大鼠出现主动脉硬化早期病变,证明实验成功复制了动脉粥样硬化早期模型。同时阳性组,加减四妙散低中高组都表现出良好的降低LDL-C,抵抗素和提升HDL-C,CGRP的作用,病理提示其病理发展较模型组有改善。结论:加减四妙散能够降低2型糖尿病模型小鼠的血糖、血脂水平,同时能够降低动脉硬化大鼠的抵抗素水平,提高降钙素基因相关肽水平,对糖尿病大血管的动脉硬化病变有干预作用。
[Abstract]:Background: type 2 diabetes mellitus type 2 diabetes mellitusus T2DMis a metabolic disease characterized by chronic hyperglycemia, which is characterized by multiple causes. Macrovascular disease is one of its main complications. The incidence of atherosclerosis of large vessels including aorta and coronary artery in type 2 diabetes patients is significantly higher than that in normal subjects, which is one of the important causes of death. Regulating blood glucose, blood lipids, and preventing or alleviating arteriopathy in early stage are the main objectives of intervention in type 2 diabetes mellitus and its macroangiopathy. Objective: to observe the intervention effect of Qingre Dishen method on blood sugar, blood lipid and aortic lesion in animal model of type 2 diabetes mellitus (T2DM), so as to provide the basis for clinical application. Methods: the experiment was divided into two parts. In the first part, the model of type 2 diabetes was established by intraperitoneal injection of streptozotocin (STZ) high fat diet. Model mice (fasting blood glucose FBG11.1mmol L 1) were randomly divided into three groups: model group, blank group, low, medium, high dose group and metformin group. Blood glucose, blood lipid and other related indexes were measured after fasting for 12 hours after 3 weeks. In the second part, 60 SD rats of SPF grade were randomly divided into six groups: blank group, positive group, model group, low dose group, middle dose group and high dose group. In addition to the blank group, 18% lard, 7% cholesterol, 1% bovine bile salt, peanut oil and gelatinized chyme were gavaged once a day in accordance with 1ml 100g-1. After 8 weeks of continuous modeling, the drug was administered and maintained at the same time. After 6 weeks of fasting, the blood samples were taken to detect the level of resistin, the content of resistin, and the pathological changes of aorta and heart. The pathological condition of aorta was observed. Results: in the first part of the experiment, compared with the blank group, the blood glucose and blood lipid levels in the model group were significantly higher than those in the control group. Compared with the model group, the levels of blood glucose in the medium and high dose groups were significantly lower than those in the model group. In the medium and high dose groups, the blood lipid content in the high dose group was significantly lower than that in the model group, but there was no significant difference between the low dose group and the low dose group in the content of serum lipids. The results of the second part of the experiment showed that compared with the blank group, the serum level of TGG Glu in the model group was higher than that in the control group, and the LDL-C content in the serum of the model group was higher than that in the control group, and the pathological findings showed that the rats with hyperlipidemia model had early lesions of aortic sclerosis. It was proved that the early model of atherosclerosis was successfully duplicated in the experiment. At the same time, the positive group, the addition and subtractive Simiao San low and high level group all showed the good effect of decreasing LDL-C, resistin and elevating HDL-Con CGRP, pathology indicated that its pathological development was improved compared with the model group. Conclusion: the addition and subtraction of Simiao Powder can decrease the level of blood glucose and blood lipid, decrease the level of resistin and increase the level of calcitonin gene-related peptide in model mice with type 2 diabetes mellitus. It can interfere with arteriosclerotic lesions of large vessels of diabetes mellitus.
【学位授予单位】：南京中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R259

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