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目的:探讨局灶节段性肾小球硬化(FSGS)大鼠转化生长因子-β_1(TGF-β_1),结缔组织生长因子(CTGF)在肾组织中的表达,检测尿液中两者的水平。观察氯沙坦对肾组织TGF-β_1、CTGF蛋白的表达及尿液两者水平的影响。方法:40只Wist- ar大鼠随机分为实验组和治疗组。采用单侧肾摘除后重复静脉注射多柔比星(ADR)制作加速FSGS大鼠动物模型。第1次注药后1周,治疗组大鼠给予氯沙坦50mg·kg~(-1)·d~(-1)灌胃,实验时间12周。于第6,12周免疫组化观察肾组织TGF-β_1、CTGF蛋白质的表达,EIISA检测尿液中两者水平。结果:与治疗组相比,实验组12周时尿液TGF-β_1、CTGF水平,肾组织内TGF-β_1、CTGF蛋白质的表达明显升高(P<0.01)。肾组织内TGF-β_1蛋白与CTGF蛋白的表达显著正相关(r=0.83,P<0.01),尿液中两者排泄量亦明显正相关(r=0.74,P<0.01)。结论:FSGS大鼠TGF-β_1、CTGF蛋白在肾组织表达及尿液中的排泄明显升高。氯沙坦可减轻肾组织TGF-β_1、CTGF蛋白的表达,减少两者尿液中的排泄而有肾保护作用。
Objective: To investigate the expression of transforming growth factor-β 1 (TGF-β 1) and connective tissue growth factor (CTGF) in renal tissue in focal segmental glomerulosclerosis (FSGS) rats and to detect the levels of both . To observe the effect of losartan on the expression of TGF-β 1, CTGF protein and urinary levels in renal tissue. Methods: Forty Wistar rats were randomly divided into experimental group and treatment group. Animal model of accelerated FSGS rats was made by repeated intravenous injection of doxorubicin (ADR) after unilateral kidney removal. One week after the first injection, the rats in the treatment group were given losartan 50 mg · kg -1 d -1 for 12 weeks. At the 6th and 12th week, the expression of TGF-β1 and CTGF protein in renal tissue was observed by immunohistochemistry. The levels of CTGF and TGF-β1 in urine were detected by EIISA. Results: Compared with the treatment group, the expression of TGF-β 1, CTGF, TGF-β 1 and CTGF protein in urine in the experimental group was significantly increased at 12 weeks (P <0.01). There was a significant positive correlation between the expression of TGF-β 1 protein and CTGF protein in renal tissue (r = 0.83, P <0.01), and the urinary excretion of TGF-β 1 (r = 0.74, P <0.01). Conclusion: The expression of TGF-β 1 and CTGF in FSGS rats is significantly increased in renal tissue and excreted in urine. Losartan can reduce the expression of TGF-β 1, CTGF protein in renal tissue and reduce the excretion of both urine and renal protection.