益肾保真方对慢性肾衰竭大鼠肾纤维化干预作用的实验研究

Experimental research on intervention effects of“Yishen Baozhen Formula”on renal fibrosis of chronic renal failure rats

目的探讨益肾保真方对慢性肾衰竭(CRF)大鼠肾纤维化的干预作用及其机制。方法采用两步分肾切除法复制5/6肾切除大鼠慢性肾衰竭模型,随机分为假手术组、模型组、益肾保真方高剂量组、益肾保真方低剂量组及尿毒清组。各组均干预6周,观察大鼠的血肌酐、尿素氮、尿蛋白定量及肾组织病理变化情况,检测肾小球硬化指数、肾组织Ⅳ型胶原含量及结缔组织生长因子(CTGF)、α-平滑肌肌动蛋白(α-SMA)的表达。结果与模型组比较,益肾保真方组尿蛋白、血肌酐、尿素氮、肾组织IV型胶原含量均显著降低,与尿毒清组比较差异无统计学意义(P>0.05);与模型组比较,益肾保真方组大鼠肾小球硬化指数降低,肾组织CTGF、α-SMA表达下调,与尿毒清组比较差异有统计学意义(P<0.05)。结论益肾保真方能延缓肾衰竭进展,干预肾纤维化进程,其机制可能与下调肾组织CTGF、α-SMA的表达,抑制肾脏固有细胞的转分化,从而减少细胞外基质成分的合成和积聚有关。

Objective To explore the intervention effects of ＂ Yishen Baozhen Formula＂ on renal fibrosis of chronic renal failure （CRF） and its therapeutic effectiveness mechanism. Methods The CRF models were replicated by two-step of 5/6 nephrectomy and randomized into sham-operated group, model group, high-dose ＂Yishen Baozhen Formula＂ group, low-dose ＂Yishen Baozhen Formula＂ group and ＂Niaoduqing＂ group, with the course of 6 weeks. The Scr, BUN, urine protein quantity and pathological changes of kidney tissues were observed, and the glomerulosclerosis index （GSI） , type 1V collagen content and expressions of CFGF and a-SMA were detected. Results Compared with the model group, the urine protein, Scr, BUN and content of type IV collagen in ＂Yishen Baozhen Formula＂ groups were decreased significantly. No significant difference was found between ＂Yishen Baozhen Formula＂ groups and ＂Niaoduqing＂ group; the GSI and expressions of CTGF and a-SMA were down-regulated, with significant differences between ＂Yishen Baozhen Formula＂ groups and ＂ Niaoduqing＂ group （P 〈 0. 05 ）. Conclusion ＂Yishen Baozhen Formula＂ can retard the progress of renal failure aggravation, interfere with the process of chronic renal failure fibrosis. Its mechanism may be related to down-regulating the expressions of CTGF and a-SMA, inhibiting the transdifferentiation of inherent kidney cells, thus to reduce the synthesis and accumulation of extracellular matrix.