伊贝沙坦对大鼠糖尿病模型肾脏肥大和肾小球毛细血管基底膜厚度的影响  

Influence of irbesartan on renal hypertrophy and thickening of glomerular basement-membrane in streptozotocin-induced diabetic rats

作　　者：刘必成[1] 罗冬冬[1] 孙静[1] 马坤岭[1] 阮雄中 

机构地区：[1]东南大学附属中大医院肾脏病研究所,南京210009 [2]英国伦敦皇家公立医院肾脏中心

出　　处：《中华内科杂志》2003年第5期320-323,共4页Chinese Journal of Internal Medicine

基　　金：江苏省自然科学基金 (7790 0 0 2 0 46) ;江苏省医学重点人才基金资助

摘　　要：目的　观察伊贝沙坦对大鼠糖尿病模型肾脏肥大和肾小球毛细血管基底膜厚度的影响。方法　将SD大鼠分为糖尿病肾病组 (A组 )、伊贝沙坦治疗组 (B组 )、健康对照组 (C组 ) ,A和B组大鼠制成糖尿病模型 ,B组予以 5 0mg/kg伊贝沙坦灌胃。观察第 4、8、12周大鼠的血糖、体重、尿白蛋白、2 4h尿蛋白的改变及第 12周时的肌酐清除率 (Ccr)、肾重、肾脏肥大指数、肾组织总蛋白含量、肾小球面积和体积、肾小球毛细血管基底膜 (GBM )厚度的改变。通过免疫组化观察肾结缔组织生长因子 (CTGF)和转化生长因子 (TGF) β1的表达。结果　A组和B组大鼠血糖较C组明显升高且维持在一个较高水平 (P <0 0 1)。A组大鼠的体重较C组明显下降 ,B组有所增加 (P <0 0 5 )。随时间的推移 (第 4、8、12周 ) ,A组大鼠尿蛋白、尿白蛋白逐渐增加 ,B组明显减少 (P <0 0 1)。A组大鼠Ccr较C组显著升高 (P <0 0 1) ,B组Ccr明显下降 (P <0 0 5 )。至第 12周时 ,A组大鼠肾脏重量、肾脏肥大指数、肾组织总蛋白含量、肾小球面积和体积均较C组明显增加 (P <0 0 1) ,B组均较A组降低 (P <0 0 1,P <0 0 5 )。免疫组化半定量分析显示 ,A组大鼠CTGF与TGF β1的表达均高于C组(P <0 0 1) ,B组明显低于A组 (P <0 0 1,P <0 0 5 )。A组大鼠GBM较C?Objective To investigate the influence of angiotensin Ⅱ receptor antagonist irbesartan (Irb) on renal hypertrophy and thickening of glomerular basement membrane (GBM) in streptozotocin (STZ) induced diabetic rats. Methods Sprague-Dalwley (SD) rats were randomly divided into three groups: normal control (group N, n =7), diabetic nephropathy (group DN, n =6) and diabetic nephropathy treated with Irb (group DNI, n =7). Diabetes was induced by injection of STZ intraperitoneally after rats had received uninephroectomy. Blood glucose (BG), body weight (BW), urinary albumin excretion (Ualb), 24-hour proteinuria (24hUpro) were observed in the rats at week 4, 8, 12 respectively. Creatinine clearance (Ccr), kidney weight (KW), profile of kidney hypertrophy (KW/BW), renal tissue protein contents (RTP), glomerular area (A_G), glomerular volume (V_G), and width of GBM were determined at week 12 when the rats were sacrificed. Renal expression of connective tissue growth factor (CTGF) and transforming growth factor-β_1(TGF-β_1) were determined by immunohistochemistry. Results There is no significant difference of BG between group DN and group DNI ( P >0.05). Irb treatment significantly prevented the increase of Ualb excretion and 24hUpro and the deterioration of Ccr in diabetic rats ( P <0.05, P <0.01 respectively). Furthermore, Irb markedly inhibited the increasing of KW, KW/BW, RTP, AG and VG shown in diabetic rats ( P <0.05, P < 0.01 respectively). More interestingly, we firstly demonstrated that Irb significantly prevented the thickening of GBM [N group: (127.50±22.14) nm, DN group: (280.38±52.77) nm, DNI group: (144.07±24.85) nm] and immunostaining for CTGF ( P <0.05 respectively). In addition, the extent of CTGF expression is positively correlated with the glomerular immunostaining for TGF-β_1 and size of V_G ( P <0.01). Conclusion This is the first data to demonstrate that Irb exerts early renal protective role in diabetic nephropathy, possibly through inhibition of renal hypertrophy and renal expression of CT

关 键 词：伊贝沙坦 大鼠 糖尿病模型 肾脏肥大 肾小球毛细血管基底膜 影响 

分 类 号：R587.1[医药卫生—内分泌] R692[医药卫生—内科学]