肾纤复元胶囊对单侧输尿管梗阻大鼠模型肾间质纤维化的抑制作用及机制探讨

目的观察肾纤复元胶囊对单侧输尿管梗阻（UUO）大鼠模型的治疗作用并探讨其机制。方法将48只SD大鼠随机分为假手术（SOR）组、UUO模型组、氯沙坦治疗组（LOS组）和肾纤复元胶囊治疗组（SXFYC组）。后三组采用经典的单侧输尿管梗阻术建立肾间质纤维化大鼠模型。观察术后第7、14天各组大鼠血尿生化指标变化、肾组织病理变化，检测转化生长因子β1（TGF—β1）、α-平滑肌肌动蛋白（α—SMA）、Ⅰ型胶原（ColⅠ）和纤维连接蛋白（FN）在肾组织中的表达及TGF-β1、α-SMA、ColⅠ和FN在基因水平的表达情况。结果不同组大鼠术后第7、14天24小时尿蛋白总量差异无显著性（P〉0．05），两治疗组血肌酐明显低于UUO模型组（P〈0．05），两治疗组间差异无统计学意义（P〉0．05）；光镜下肾组织病理切片显示两治疗组与同一时间点UUO模型组相比，肾间质纤维化程度显著降低（P〈0．05），两治疗组间差异无统计学意义（P〉0．05）；免疫组化和RT—PCR结果表明，两治疗组各时间点TGF—β1、α—SMA、ColⅠ和FN的表达均低于UUO模型组（P〈0．05），两治疗组间差异无统计学意义（P〉0．05）。结论肾纤复元胶囊可从一定程度上减轻UUO大鼠肾间质纤维化程度，其作用机制可能与下调TGF—β1和α—SMA表达、抑制ColⅠ和FN的合成有关。

Effect and its mechanism of "Shenxian Fuyuan Capsule" on the renal interstitial fibrosis of unilateral ureteral Obstruction rat model

To observe the therapeutic effect of ＂Shenxian Fuyuan Capsule＂ （SXFYC） on the renal interstitial fibrosis of unilateral ureteral obstruction （UUO） rat model, and then to study its possible mechanism. Methods Forty-eight Sprague-Dawley male rats were randomly divided into four groups：sham-operation group（SOR group ）, unilateral ureteral obstruction group （UUO group）, losartan treatment group （LOS group） and SXFYC treatment group （SXFYC group）. On the 7th day and 14th day after operation, we observed the pathologic change of the kidney and detected serum creatinine and proteinuria. The expression levels of TGF-β1 （transforming growth factor- β1 ）, α-SMA（α-smooth muscle actin）, ColⅠ（collagen Ⅰ） and FN （fibronectin）were detected by immunohistochemistry and real-time polymerase chain reaction （RT-PCR） at each time point. Results On the 7th day and 14th day after operation, there was no significant difference in the level of proteinuria among groups at the same time point （P〉0. 05）. The level of serum creatinine in UUO group was obviously higher than that in losartan treatment group and SXFYC treatment group （P〈0. 05）. The damage of renal interstitium of UUO group was heavier than that of SXFYC and losartan treatment groups at the same time point （P〈0. 05） and there were no significant differences between the SXFYC and losartan treatment groups （P〉0. 05）. Immunohistochemistry and RT-PCR showed that the expression level of TGF-β1, α-SMA, ColⅠ and FN in SXFYC and losartan treatment groups were lower than that in UUO group on the 7th day and 14th day after operation （P〈0. 05） and there were no significant differences between the SXFYC and losartan treatment groups （P〉0.05）. Conclusion ＂Shenxian Fuyuan Capsule＂ can partly delay the progress of renal interstitial fibrosis in UUO rat model. Its mechamnism may be related to suppressing the expression of TGF-β1 ,α-SMA and reducing the composition of ColⅠ and FN.