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目的 探讨血管紧张素 II受体拮抗剂伊贝沙坦 (Irbesartan,Irb)对链脲佐菌素 (Streptozotocin,STZ)诱导的糖尿病大鼠结缔组织生长因子 (connective tissue growth factor ,CTGF)表达的影响。方法 将 SD大鼠随机分为正常对照 (N)组、糖尿病肾病 (DN)组、Irb治疗 (DNI)组。腹腔注射 STZ诱导糖尿病模型 ,观察治疗后第4、8、1 2周血糖、体重、尿白蛋白排泄量 (2 4h Ualb)、尿总蛋白排泄量 (2 4h Upro)的变化 ,并观察 1 2周时肌酐清除率(Ccr)、肾小球硬化程度 (GS)的改变 ,免疫组织化学方法分析肾皮质 CTGF、转化生长因子β1 (TGF-β1 )的表达。结果 DN组 2 4h Ualb、2 4h Upro的排泄量较 N组明显增加 (P<0 .0 1 ) ,Ccr明显增高 (P<0 .0 1 ) ,DNI组 2 4h Ualb、2 4h Upro和 Ccr较 DN组显著减少 (P<0 .0 1 )。 DN组肾小球硬化程度较 N组增高 (P<0 .0 1 ) ,Irb可显著减轻肾小球硬化程度 (P<0 .0 1 )。DN组肾皮质 CTGF和 TGF-β1 的表达较 N组增高 (P<0 .0 1 ) ,Irb能明显抑制两者的表达(P<0 .0 5 ,P<0 .0 1 )。另外 ,肾皮质 CTGF的表达与 TGF-β1 呈显著正相关关系 (P<0 .0 5 )。结论 早期应用 Irb对 STZ诱导的糖尿病大鼠有肾保护作用 ,可能与抑制糖尿病大鼠肾皮质 CTGF的表达有关
Objective To investigate the effect of Irbesartan (Irb), an angiotensin II receptor antagonist, on the expression of connective tissue growth factor (CTGF) induced by streptozotocin (STZ) in diabetic rats . Methods SD rats were randomly divided into normal control group (N), diabetic nephropathy (DN) group and Irb treatment group (DNI). The model of STZ-induced diabetes mellitus was injected intraperitoneally. The changes of blood glucose, body weight, urinary albumin excretion (24 h Ualb) and urinary total protein excretion (24 h Upro) were observed at 4, 8 and 12 weeks after treatment. (Ccr) and glomerular sclerosis (GS) were measured. The expression of CTGF and TGF-β1 in renal cortex were analyzed by immunohistochemical method. Results The excretion of 24 hours Ualb and 24 hours Upro in DN group was significantly higher than that in N group (P <0.01), Ccr was significantly increased (P <0. 01), DNU 24 hours Ualb, 24 hours Upro and Ccr Compared with DN group significantly decreased (P <0.01). The severity of glomerulosclerosis in DN group was higher than that in N group (P <0.01). Irb significantly reduced the degree of glomerulosclerosis (P <0.01). The expression of CTGF and TGF-β1 in renal cortex of DN group was higher than that of N group (P <0.01). Irb significantly inhibited the expression of both CTGF and TGF-β1 (P <0.05, P <0.01). In addition, renal cortical CTGF expression was positively correlated with TGF-β1 (P <0.05). Conclusion Early application of Irb has a protective effect on STZ-induced diabetic rats, which may be related to the inhibition of CTGF expression in renal cortex of diabetic rats