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目的:通过研究中药复方——肾衰泻浊丸对单侧输尿管梗阻(UUO)大鼠肾间质核转录因子κB(NF-κB)、骨桥蛋白(OPN)、肝细胞生长因子(HGF)表达的影响,探讨其抗肾间质纤维化的机制。方法:建立UUO大鼠模型,72只成年雄性Wistar大鼠随机分为假手术组、模型组、贝那普利组及肾衰泻浊丸低、中、高剂量组。在不同的时间点(14、21、28d)检测每组4只实验大鼠治疗后的血清尿素氮(BUN)、肌酐(Scr)变化。观察梗阻侧肾脏病理变化;采用免疫组化法检测肾组织中的NF-κB、HGF及OPN的表达;RT-PCR法检测肾组织中OPNmRNA的表达水平。结果:与假手术组相比,模型组大鼠血清BUN、Scr水平、NF-κB、OPN表达显著升高,HGF表达减少差异有统计学意义(P<0.01,P<0.05);与模型组相比,各治疗组血BUN、Scr水平、NF-κB、OPN表达均显著降低,HGF表达均有所增多差异有统计学意义(P<0.01,P<0.05)。肾衰泻浊丸能够明显降低UUO大鼠血BUN、Scr水平,减轻肾间质损伤,明显下调肾组织中NF-κB和OPN的表达、上调HGF的表达,与贝那普利组比较差异有统计学意义(P<0.01,P<0.05)。结论:肾衰泻浊丸可能通过改善肾功能、抑制NF-κB、OPN的表达、诱导HGF的高表达,从而改善肾间质纤维化。
OBJECTIVE: To investigate the effect of Shenshuixiangzhuo Pill on the expression of NF-κB, osteopontin (OPN) and hepatocyte growth factor (HGF) in renal interstitium of rats with unilateral ureteral obstruction (UUO) Expression of the impact of its anti-renal interstitial fibrosis mechanism. Methods: UUO rats were established. Seventy-two adult male Wistar rats were randomly divided into sham-operation group, model group, benazepril-treated group and low-dose, middle-dose and high-dose group. Serum urea nitrogen (BUN) and creatinine (Scr) were measured at different time points (14, 21, 28d) after treatment in 4 experimental rats in each group. The pathological changes of obstructed kidney were observed. The expression of NF-κB, HGF and OPN in renal tissues was detected by immunohistochemistry. The expression of OPN mRNA in renal tissues was detected by RT-PCR. Results: Compared with sham operation group, serum BUN, Scr, NF-κB and OPN expression in model group were significantly increased (P <0.01, P <0.05) Compared with the control group, the levels of BUN, Scr, the expressions of NF-κB and OPN were significantly decreased and the expressions of HGF in all treatment groups were significantly increased (P <0.01, P <0.05). Compared with benazepril group, Shenfexiaozhuo Wan could significantly decrease the levels of BUN and Scr in blood and renal interstitium in UUO rats, decrease the expressions of NF-κB and OPN, and up-regulate the expression of HGF in renal tissues Statistical significance (P <0.01, P <0.05). Conclusion: Shenshuaxiangzhao Pill can improve renal interstitial fibrosis by improving renal function, inhibiting the expression of NF-κB and OPN and inducing the high expression of HGF.