HTG和糖尿病复合地鼠模型的建立及诱发肾损伤机制研究

发布时间：2018-03-18 01:16

本文选题：糖尿病　切入点：甘油三酯　出处：《吉林大学》2009年博士论文　论文类型：学位论文

【摘要】： 现已证实高甘油三酯血症是动脉粥样硬化等多种心脑血管疾病的独立危险因子,目前富含甘油三酯的脂蛋白对肾脏的致病性也逐渐得到重视,本研究首次建立糖尿病高甘油三酯血症金黄地鼠模型,并探讨了高甘油三酯对肾脏的损伤机制。采用链脲佐菌素注射联合高脂高胆固醇饮食饲喂的方法,诱导地鼠肝脏甘油三酯分泌增加,清除减慢,血浆甘油三酯显著升高,建立了饮食诱导的非转基因高甘油三酯血症动物模型。通过对此模型血液流变学、肾功能、肾脏病理组织学变化等的检测,发现动物出现蛋白尿、肾脏肥大、肾小球系膜基质扩张、糖原沉积等肾脏病理改变,表明高甘油三酯在诱发早期糖尿病肾损伤中发挥着重要的作用。进一步研究发现高甘油三酯致肾损伤的机制为脂代谢关键基因SREBP-1c表达上调、TGF-β通路活化及氧化应激增加,导致高甘油三酯血症引发肾脏损伤。SREBP-1c表达的上调引起地鼠脂肪酸合成增加,脂质沉积于肝脏、肾脏,启动了肾损害的关键步骤,同时致纤维化生长因子TGF-β、CTGF、PAI-1及炎性因子IL-6、TNF-α上调,证实高甘油三酯血症通过激活TGF-β通路导致肾小球病变,另外,高甘油三酯血症加速了高糖所致的氧化应激,形成丙二醛等脂质过氧化物加速肾脏损伤。
[Abstract]:It has been proved that hypertriglyceridemia is an independent risk factor for many cardiovascular and cerebrovascular diseases such as atherosclerosis. In this study, the diabetic hypertriglyceridemia golden hamster model was established for the first time, and the mechanism of renal damage induced by hypertriglyceridemia was investigated. The method of streptozotocin injection combined with high fat and high cholesterol diet was used. The liver triglyceride secretion was increased, clearance was slowed down, plasma triglyceride was significantly increased in hamster liver. An animal model of non-transgenic hypertriglyceridemia induced by diet was established. Histopathological changes of the kidney were detected, including proteinuria, renal hypertrophy, glomerular Mesangial matrix dilatation, glycogen deposition and other renal pathological changes. It is suggested that high triglyceride plays an important role in early diabetic renal injury. It is found that the mechanism of high triglyceride induced renal injury is the up-regulation of SREBP-1c expression of lipid metabolism key gene and the activation of TGF- 尾 pathway and the increase of oxidative stress. The up-regulation of the expression of SREBP-1c induced by hypertriglyceridemia increased the synthesis of fatty acids in hamsters, and the lipid deposition in the liver and kidney initiated the key steps of renal damage, at the same time, the expression of fibrosis growth factor TGF- 尾 CTGFGFPAI-1 and the inflammatory factor IL-6 TNF- 伪 were upregulated. Hypertriglyceridemia leads to glomerular lesion by activating TGF- 尾 pathway. In addition, hypertriglyceridemia accelerates oxidative stress induced by hyperglycemia and forms lipid peroxide such as malondialdehyde to accelerate renal injury.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2009
【分类号】：R587.1;R-332

【相似文献】