曲尼司特联合贝拉普利对5／6肾切除大鼠肾脏的保护作用

Protective effects of tranilast combined with benazepril on the renal disease progression in rats with 5/6 nephrectomy

目的观察曲尼司特联合贝拉普利对5／6肾切除大鼠肾脏的保护作用，并探讨其机制。方法将50只雄性SD大鼠随机分为5组：假手术组（S组）、5／6肾切除模型组（M组）、曲尼司特干预组（T组）、贝拉普利干预组（B组）和曲尼司特联合贝拉普利干预组（C组），每组10只。术后第12周观察各组大鼠体重、血压、尿蛋白量、血肌酐及肾组织病理改变，用逆转录聚合酶链反应（RT-PCR）法检测残肾组织转化生长因子β1（TGF-β1）mRNA的表达，Western blotting法检测残肾组织Ⅲ型胶原蛋白的表达。结果与S组相比，M组大鼠血压、尿蛋白量和血肌酐水平明显升高，肾小球硬化、肾间质纤维化程度加重，残肾组织TGFβ1 mRNA和Ⅲ型胶原蛋白的表达升高，差异均有统计学意义（P〈0．05）。与M组相比，T组和B组上述指标减轻，差异均有统计学意义（P〈0．05）。与T组和B组相比，C组均更明显地减轻上述指标，差异均有统计学意义（P〈0．01）。结论曲尼司特联合贝拉普利对5／6肾切除大鼠的肾脏有更佳的保护作用，其机制可能与其减轻TGF-β1引起的细胞外基质的沉积有关。

Objective To observe the protective effects of tranilast combined with benazepril on the renal disease progression in rats with 5/6 nephrectomy, and to explore its mechanism. Methods Fifty SD rats were randomly divided into 5 groups： sham-nephrectomized group （group S）, 5/6 nephrectomy group （group M）, tranilast treatment group （group T）, benazepril treatment group （group B）, combination with tranilast and benazepril treatment group （group C）. Rats were sacrificed at the end of the 12 th week. The body weight, blood pressure, proteinuria, and serum creatinine were measured at the end of the experiment. Renal pathological changes were observed by immunohistochemistry, the reverse transcription polymerase chain reaction was used to detect the mRNA expression of transforming growth factor-β1 （TGF-β1）, and Western blot was applied to assay the protein expression of collagen Ⅲ. Results As compared with group S, blood pressure, proteinuria, the serum creatinine, glomerulosclerosis, interstitial fibrosis, the mRNA level of TGF-β1, and protein level of Collagen Ⅲ were all increased in group M （P〈0. 05）. These above manifestations were all attenuated by treatment with either tranilast or benazepril. As compared with group T and group B, the group C provided additional and incremental improvements in above manifestations （P 〈 0. 01 ）. Conclusions Combination of tranilast and benazepril was superior to single-agent treatment on kidney structure and function in 5/6 nephrectomy model. The mechanism may be related to that tranilast can decrease the expression of TGF-β, resulting extracellular matrix production in the kidney.