转化生长因子β_1在肾间质纤维化大鼠模型中的表达及意义

The expression and significance of transforming growth factor-β_1 in rats with renal tubulointerstitial fibrosis

目的了解转化生长因子-β1(transforming growth factor-β1,TGF-β1)在肾小管间质纤维化中的表达及其意义;探讨及比较科素亚及霉酚酸酯的肾脏保护作用及可能的作用机制。方法采用单侧输尿管结扎术(unilateral ureteral obstruction,UUO)建立肾小管间质纤维化大鼠模型。将大鼠随机分为4组:假手术组、模型组、科素亚治疗组[30mg/(kg.d)]、霉酚酸酯治疗组[20mg/(kg.d)]。手术后第9天处死各组大鼠,分别经免疫组化方法观察各组大鼠肾组织的TGF-β1的表达部位、表达水平及α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)的表达情况;HE及Masson染色评定各组肾小管间质损害程度。结果模型组TGF-β1、α-SMA的表达及肾小管间质损伤指数明显高于假手术组(P<0.05);而科素亚治疗组、霉酚酸酯治疗组均明显低于模型组(P<0.05);科素亚治疗组与霉酚酸酯治疗组相比,各项指标差异均无统计学意义(P>0.05);TGF-β1与肾小管间质损伤指数(r=0.788,P<0.01)及α-SMA(r=0.940,P<0.01)呈正相关。结论TGF-β1在肾小管间质纤维化的病程进展中起重要的促进作用。而科素亚、霉酚酸酯则可能通过下调TGF-β1的表达而达到防治肾小管间质纤维化的作用。

Objective To investigate the expression of transforming growth factor-β1 in rats with renal tubulointerstitial fibrosis and the effects of losartan potassium tablet and mycophenolate mofetil on the process of the fibrosis. Methods Nine days after unilateral ureteral obstruction （UUO） animal models were made, the expressions of TGF-β1 and a-smooth muscle ac- tin in the obstructed kidney were measured by immunohistochemistry method respectively. At the same time, the degree of tubu- lointerstitial damage was scored. Results The levels of TGF-β1 and a-smooth muscle actin in the model group increased remark- ably compared with the sham-operated group （P〈0. 01） and were parallel to the degree of tubulointerstitial damage. In compa- rison with the groups treated with losartan potassium tablet and mycophenolate mofetil, the levels of TGF-β1 and a-smooth mus- cle actin were significantly decreased by both losartan potassium tablet and mycophsnolate mofetil. TGF-β1 had positive correla- tion with the index of tubulointerstitial damage and a-smooth muscle actin. Conclusions TGF-β1 may play an important role in the development of renal tubulointerstitial fibrosis. Losartan potassium tablet and mycophenolate mofetil may prevent the fibrosis development partly via down-regulating the expression of TGF-β1.