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福辛普利保护糖尿病肾病及其对肾组织TGFβ_1 mRNA表达的影响 被引量:4

The renoprotective effect of fosinopril and its effect on TGFβ_1 mRNA expression in renal tissue in diabetic rats
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摘要 目的探讨福辛普利对糖尿病肾小球病变的保护作用与机制。方法建立糖尿病大鼠模型,分为正常对照组(A组)、糖尿病组(B组)、福辛普利治疗组(C组),C组1 w后给予福辛普利灌胃给药。检测各组第1、2、4、12周血糖、24 h尿视黄醇结合蛋白以及尿白蛋白排泄率;分别于第4、12周每组各处死5只大鼠,计算肾脏肥大指数,检测皮质TGFβ1mRNA水平;检查肾小球基底膜、系膜区病理改变。结果第1周B和C组尿白蛋白排泄率与A组差异无统计学意义;第2、4、12周尿白蛋白和视黄醇结合蛋白排泄率,B组均显著高于A组;第4、12周,B组大鼠肾皮质TGFβ1mRNA表达较A组显著增加,C组TGFβ1mRNA表达明显低于B组,但较A组表达量仍然增加;B组肾小球毛细血管基底膜增厚;C组肾小球毛细血管基底膜也有不规则增厚,较同时期B组减轻。结论肾脏TGFβ1mRNA表达的上调可能是糖尿病肾病的发生机制之一,福辛普利对糖尿病肾病具有确切的保护作用。 Objective To observe the renoprotective effects of angiotensin converting inhibitor (ACEI)-fosinopril and explore its renoprotective mechanism among diabetic rats. Methods Normal control rats (group A) ; diabetic rats (group B), fosinopril rats (group C) were studied. Blood glucose, urinary albumin and retinal-binding protein (RBP) excretion rates were measured at the 1st, 2nd, 4th and 12th week, as well as the expressions of TGFβ1 mRNA in renal cortex and the relative kidney index (ratio between kidney weight and body weight) at the 4th and 12th week. Renal pathplogy of diabetic rats was observed at the 4th and 12th week. Results At the 1st week(no treatment given), the urinary excretion rates of albumin in group 13 and C were similar to that in group A. At the 2nd, 4th and 12th week, the urinary excretion rates of albumin and RBP in group 13 were higher than that in group A. The expression of TGF-β, mRNA in.renal cortex in group C was significantly lower than that in group B; the expression of TGFβ1 mRNA in renal cortex in group B was much higher than that in group A; the electron microscopy showed significant mesangial expansion, glomerular basement membrane thickening in group B, but these abnormal changes were alleviated to a certain extent in group C. Conclusions The overexpression of TGFβ1 mRNA in renal cortex of diabetic rats may be one of the mechanisms of diabetic nephropathy; fosinopril had certain renoprotective effects.
出处 《疾病控制杂志》 2006年第3期262-266,共5页 Chinese Journal of Disease Control and Prevention
基金 安徽省自然科学基金资助课题(01041181)
关键词 糖尿病 转化生长因子Β Diabetes mellitus Transforming growth factor beta
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参考文献6

  • 1Leehey DJ, Singh AK, Alavi, et al. Role of angiotensin Ⅱ in diabetic nephropaty [J]. Kidney Int, 2000,77 : S93-S98.
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同被引文献27

  • 1章晓燕,刘芳,贾伟平.α-硫辛酸与糖尿病周围神经病变[J].国外医学(内分泌学分册),2005,25(4):262-264. 被引量:146
  • 2王迎新,李远思,陈燕,叶山东.福辛普利与氯沙坦对实验性糖尿病大鼠肾病的防治作用与转化生长因子β_1的关系[J].中国药理学通报,2005,21(7):884-888. 被引量:11
  • 3常虹,叶山东,范爱红,陈燕,李远思.血管内皮生长因子与糖尿病肾病关系的实验性研究[J].安徽医科大学学报,2005,40(6):523-528. 被引量:4
  • 4Ota T,Takamura T,Ando H,et al. Preventive effect of cerivastatin on diabetic nephropathy through suppression of glomerular macrophage recruitment in a rat model. Diabetologia, 2003, 46 : 843-851.
  • 5Volpini RA, da Silva CC, Costa RS, et al. Effect of enalapril and losartan on the events that precede diabetic nephropathy in rats. Diabetes Metab Res Rev, 2003, 19:43-51.
  • 6Schrijvers BF, Flyvbjerg A, De V riese AS. The role of vascular endothelial growth factor (VEGF) in renal pathophysiology [J]. Kidney Int, 2004,65(6) :2003-2017.
  • 7Hoshi S, Nomoto K, Kuromitsu J, et al. High glucose induced VEGF expression via PKC and ERK in g|omeru|ar podocytes [J]. Biochem Biophys Res Commun, 2002,290 ( 1 ) : 177-184.
  • 8Kang YS, Park YG, Kim BK, et al. Angiotensin Ⅱ stimulates the synthesis of vascular endothelial growth factor through the p38 mitogen activated protein kinase pathway in cultured mouse podocytes [J]. J Mol Endocrinol, 2006,36(2):377-388.
  • 9Lee EY, Chung CH, Kim JH, et al. Antioxidants ameliorate the expression of vascular endothelial growth factor mediated by pro- tein kinase C in diabetic podocytes [J]. Nephrol Dial Transplant, 2006,21(6) : 1496-1503.
  • 10Toblli JE, Ferrini MG, Cao G, et al. Antifibrotic effects of pi- oglitazone on the kidney in a rat model of type 2 diabetes mellitus [ J]. Nephrol Dial Transplant, 2009,24 (8) : 2384-2391.

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