代谢综合征小鼠模型的建立及中药复方干预

发布时间：2018-08-06 18:41

【摘要】： 代谢综合征(MS)是一系列存在内在联系的心血管疾病(CVD)和2型糖尿病(T2DM)危险因素的集结,包括腹部肥胖、血脂异常、促炎症状态、胰岛素抵抗(IR)、糖尿病相关的多种代谢异常成分。MS的发病机制尚不完全清楚,目前认为遗传多基因的易感性和环境因素共同参与其发病过程,其中高脂高热量饮食摄入及运动减少作为MS发病的环境因素备受重视。因此,我们选择具有饮食诱导成肥胖、T2DM、动脉粥样硬化的C57BL/6J小鼠作为模式生物,通过高脂高热量纯化饲料这一环境因素作为诱导方法,制备MS动物模型。另外,由于目前MS的药物治疗原则主要是针对具体的代谢紊乱,缺乏有效的整体治疗方案。因此,我们在MS小鼠模型的基础上探寻被称为天然组合化学库、具有多靶点作用特点的中药复方(三组)对MS的干预效应。我们发现在以高脂高热量饲料喂养C57BL/6J小鼠喂养1周时,与普食对照组相比,模型组小鼠体重(BW)出现显著性升高(P＜0.001),并表现为中心型肥胖。4周时空腹血糖(FBG)显著性升高(P＜0.01),腹腔注射糖耐量试验(IPGTT)曲线显示糖耐量降低。6周时出现高胰岛素血症,提示胰岛素抵抗(IR)。10周时血清TC、HDL-C、TG、TG、HDL-C、LDL-C、FFA均显著性升高(P＜0.01或0.001)。BW增加与糖脂代谢紊乱的上述指标均存在高度正相关关系。这表明MS小鼠模型的成功建立。在造模完成后我们进行了三组中药复方对上述指标的疗效观察。研究发现二陈汤加减能有效降低模型小鼠体重、肝脏及内脏脂肪重量、IPGTT试验中的120min时血糖、FBG、脂代谢紊乱的FFA、TG、LDL-C水平。栀黄汤加减也有类似效果,但实验中发现小鼠出现脱毛情况,这可能与该方中含泻热清肠之大黄,有关。平胃散加减仅表现出轻微的降低BW、FBG、TG效果。总之,本研究中我们成功建立了造模方法简单易行、周期较短、稳定性好、可重复性高与人类MS自然发病过程类似的MS小鼠模型;在该模型基础上筛选出二陈汤加减方能够有效改善MS的代谢紊乱状态,提示健脾祛湿、行气活血的中医药治疗大法可能是MS的有效整体治疗方案。
[Abstract]:Metabolic syndrome (MS) is a collection of intrinsically linked risk factors for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), including abdominal obesity, dyslipidemia, and proinflammatory status. The pathogenesis of various metabolic abnormalities related to insulin resistance (IR), diabetes. Ms is not fully understood. It is believed that the susceptibility of genetic polygenes and environmental factors are involved in the pathogenesis of insulin resistance diabetes mellitus. Among them, high fat and high calorie diet intake and exercise reduction as the environmental factors of MS disease have been paid more attention. Therefore, we selected C57BL/6J mice with diet to induce obesity and atherosclerosis as model organisms, and made MS animal model by high fat and high calorie purified feed. In addition, due to the current principle of MS drug therapy is directed to specific metabolic disorders, there is a lack of effective overall treatment. Therefore, on the basis of MS mouse model, we explore the intervention effect of traditional Chinese medicine compound (group 3), which is called natural combinatorial chemistry library and has the characteristics of multi-target action, on MS. We found that when C57BL/6J mice were fed with high fat and high calorie diet for 1 week, they were compared with the normal diet control group. In the model group, the body weight (BW) increased significantly (P < 0.001), and the fasting blood glucose (FBG) increased significantly at 4 weeks after central obesity (P < 0. 01). The (IPGTT) curve of the intraperitoneal glucose tolerance test showed that the glucose tolerance decreased 6 weeks and the hyperinsulinemia occurred at the same time. It was suggested that the serum TCCH HDL-CU LDL-CfFA increased significantly at 10 weeks after insulin resistance (P < 0. 01 or 0.001). There was a high positive correlation between the increase of serum TCU HDL-CU and the above indexes of glycolipid metabolism disorder (P < 0. 01 or 0.001). This indicated that MS mouse model was successfully established. After the establishment of the model, we observed the curative effect of three groups of traditional Chinese medicine compound on the above indexes. It was found that the addition and subtraction of Erchen decoction could effectively reduce the levels of FBG and FFA-TGG LDL-C in 120min of model mice, liver and visceral fat weight in IPGTT test. Zhihuang decoction had a similar effect, but it was found that the mice had depilation in the experiment, which may be related to the rhubarb containing purging heat and clearing the intestines. The addition and subtraction of Pingwei Powder only showed a slight effect of decreasing the TG of BWN FBGG. In conclusion, in this study, we successfully established a model of MS mouse model, which is simple and easy, short cycle, good stability, high reproducibility and similar to the natural process of human MS. On the basis of this model, Erchen decoction plus subtractive prescription can effectively improve the metabolic disorder of MS, suggesting that the traditional Chinese medicine therapy of invigorating spleen and removing dampness and activating qi and promoting blood circulation may be an effective overall treatment scheme for MS.
【学位授予单位】：中国协和医科大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R-332;R285.5

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