【作者】 王昕；

【导师】 刘超；

【作者基本信息】 南京医科大学 ， 内分泌， 2004， 硕士

【摘要】 目的 1．在体外观察高浓度与低浓度葡萄糖对肾小球系膜细胞增生的影响，并观察他汀类药物阿妥伐他汀，辛伐他汀以及血管紧张素受体拮抗剂氯沙坦对高糖诱导的肾小球系膜细胞过度增殖的影响； 2．体内实验观察STZ诱导的糖尿病大鼠8周时的肾脏病变情况以及辛伐他汀及氯沙坦的治疗作用。 方法 1．肾小球系膜细胞分别培养于低糖(5.6mmol／L)或加入不同浓度刺激药物的高糖(30mmol／L)的环境中，用MTT法检测系膜细胞增殖情况； 2．观察注射链脲霉素造成的糖尿病大鼠模型在成模8周后肾脏的病理改变、结缔组织生长因子的表达情况以及尿转化生长因子的排泄量的改变与24h尿总蛋白排泄量的改变，并分别观察与比较辛伐他汀与氯沙坦对脏损害的影响。 结果 1．他汀类药物辛伐他汀、阿妥伐他汀以及血管紧张素受体拮抗剂氯沙坦均能够有效抑制高糖诱导的肾小球系膜细胞的过度增殖， 南川公科人学硕}一学位论文且在一定范围内呈现出剂量依赖与时间依赖关系; 2.辛伐他汀与氛沙坦均能够有效减轻STz诱导的糖尿病大鼠的肾脏病变，抑制结缔组织生长因子的过度表达，减少尿转化生长因子与尿总蛋白质的排泄。 结论 1.在体外，他汀类药物辛伐他汀、阿妥伐他汀以及低剂量的血管紧张素受体拮杭剂氯沙坦可以抑制高糖诱导的系膜细胞的过度增生; 2.辛伐他汀及氯沙坦可能通过抑制TGF以及CTGF的表达与分泌实现肾脏保护作用，这就为早期防治糖尿病肾病提供了新的思路。更多还原

【Abstract】 Objective: (1) To compare the effect of high concentration glucose and low concentration glucose on the proliferation of mesangial cells and to investigate the inhibiting effects of HMG-CoA reductase inhibitor atorvastatin, simvastatin and angiotensin receptor blockade losartan on the over-proliferation of mesangial cells exposed to the high concentration glucose. (2) To investigate the early nephropathy in the streptozotocin induced diabetic rats in vivo and the treatment effect of simvastatin and losartan on the early diabetic nephropathy in the streptozotocin induced diabetic rats.Methods: (1) The mesangial cells were cultured in the low glucose medium (glucose concentration is 5.6mmol/L) and high glucose medium (glucose concentration is 30mmol/L) treated by different concentration of atorvastatin, simvastatin and losartan. The cell proliferation was determined by the MTT method. (2) The diabetic S-D rats were induced by injection of streptozotocin, and then were randomly classified to the simvastatin treated, losartan treated orcontrol group. Eight weeks after the onset of hyperglycemia, the rats were sacrificed and the ratio of whole kidney to body weight , the structure damage of the kidney, the expression of the connective tissue growth factor, the urinary TGF- 1 excretion and the 24 hours urinary protein were measured.Results: (1) the high concentration glucose induces the over proliferation of mesangial cells and atorvastatin, simvastatin and losartan inhibit the over proliferation in a dose-dependent and time-dependent way. (2) The diabetic control rats showed enlarged kidney/body weight ratio, renal structure damage, increased urinary excretion of TGF- 1 and protein, while simvastatin and losartan prevented these changes.Conclusion: (1) Atorvastatin, simvastatin and losartan can inhibit the over proliferation of mesangial cells induced by the high concentration glucose; (2) Simvastatin and losartan can prevent the development of diabetic nephropathy through inhibition of expression of CTGF and inhibition of secretion of TGF- 1.更多还原