肾纤复元胶囊延缓5/6肾切除大鼠肾衰进展机制的实验研究

Experimental Study of the Therapeutic Effect and Mechanism of “Shenxian Fuyuan Capsule” on Chronic Renal Failure in Rats

目的探讨中药复方制剂“肾纤复元胶囊”治疗慢性肾功能衰竭的作用机制。方法将Wistar大鼠随机分为模型组、肾纤复元胶囊治疗组、氯沙坦治疗组与假手术组,前三组以5/6肾切除方法建立肾衰模型。分别于建模后4、8、12周检测各组鼠血尿生化指标、残肾组织α-SMA、型胶原和结缔组织生长因子(CTGF)的表达。结果两治疗组4、8、12周血BUN、Cr、24h尿蛋白定量明显低于模型组(P<0.01),治疗组之间差异无统计学意义(P>0.05);光镜下肾组织病理切片显示治疗组损害轻于模型组,其α-SMA及型胶原染色阳性面积亦低于模型组(P<0.01),治疗组之间差异无统计学意义(P>0.05);治疗组残肾组织CTGF表达低于模型组(P<0.01),治疗组之间差异无统计学意义(P>0.05)。结论“肾纤复元胶囊”通过下调CTGF在残肾组织的表达,抑制细胞外基质的积聚和细胞转分化,防止肾纤维化,对5/6肾切除后的大鼠残肾组织有明显保护作用。

Objective To study the therapeutic effect and mechanism of ＂Shenxian Fuyuan Capsule＂ （SXFYC） on chronic renal failure in rats with 5/6 nephrectomy. Methods The animal model with chronic renal failure was established by using the method of 5/6 nephrectomy. The animals were randomly divided into four groups; SXFYC treatment group, losartan treatment group, control group and pseudo-operation group （normal group）. Since the next day after operations, the rats in the SXFYC treatment group and the losartan treatment group had been intragastrically administrated with SXFYC 300 mg/kg · d and losartan 150 mg/kg · d respectively. The rats in the normal group and control group were fed with sodium chloride twice a day. Four, eight and twelve weeks later, histological and biochemical tests were undertaken to examine changes of the remnant kidney such as a-SMA, collagen Ⅰ, blood urea nitrogen, serum creatinine and proteinuria. The connective tissue growth factor （CTGF） mRNA was detected by semi-quantitative reverse transcription polymerase chain reaction （RT-PCR）. Results Both SXFYC and losartan ameliorated the histological change of remnant kidney, decreased the level of CTGF mRNA, serum creatinine and proteinuria （P〈0. 01）. There were no significant differences between the SXFYC and losartan treatment groups （P〉0. 05）. Conclusion ＂Shenxian Fuyuan Capsule＂ can improve the renal function of the 5/6 nephrectomized rats. It performs as well as losartan. ＂Shenxian Fuyuan Capsule＂ might have played an important role in preventing CTGF-mediated renal fibrosis in the 5/6 nephrectomized rats.