固本泄浊饮对5/6肾切除肾衰竭大鼠TGF-β1、BMP-7表达的影响研究

Effects of Guben Xiezhuo Decoction on TGF-β1 and BMP-7 Expressions in 5/6 Nephrectomy Rats with Renal Failure

目的分析固本泄浊饮对5/6肾切除慢性肾衰竭(CRF)大鼠转化生长因子β1(TGF-β1)、骨形态发生蛋白质-7(BMP-7)表达的影响。方法将60只Wistar大鼠随机分为6组,即正常组,假手术组,模型组,中药(固本泄浊饮)低、中、高剂量组,每组10只,除正常组外,其余5组均采用5/6肾切除术制作CRF模型,假手术组同期作两次手术,但不作肾组织切除。药物干预8周后,采血测定大鼠血肌酐(Scr)、尿素氮(BUN)和血红蛋白(HGB)水平,同时采用免疫组织化学法测定各组大鼠肾组织TGF-β1、BMP-9表达,分析其延缓CRF大鼠肾衰竭的机制。结果与正常组比较,其余各组Scr和BUN均上升(P<0.05)。与假手术组比较,模型组、中药各剂量组Scr和BUN均上升(P<0.05)。与模型组比较,中药各组Scr和BUN降低(P<0.05)。中药高、中剂量组BUN低于小剂量组,且高剂量组低于中剂量组(P<0.05)。与正常组和假手术组比较,其余各组HGB降低(P<0.05)。与模型组比较,中药各组HGB上升(P<0.05)。中药高、中剂量组HGB高于低剂量组,高剂量组高于中剂量组(P<0.05)。与正常组和假手术组比较,其余各组TGF-β1灰度值降低,BMP-7灰度值上升(P<0.05)。与模型组比较,中药各剂量组TGF-β1灰度值上升,BMP-7灰度值降低(P<0.05)。中药高剂量、中剂量组TGF-β1灰度值高于低剂量组,BMP-7灰度值低于低剂量组(P<0.05)。高剂量组TGF-β1灰度值高于中剂量组,BMP-7灰度值低于中剂量组(P<0.05)。结论固本泄浊饮可通过下调TGF-β1蛋白表达及上调BMP-7蛋白表达来延缓肾衰大鼠肾间质纤维化进展,改善肾功能。

Objective To analyze effects of Guben Xiezhuo decoction on transforming growth factor β1（ TGF-β1） and bone morphogenetic protein 7（ BMP-7） expressions in 5 /6 nephrectomy rats with chronic renal failure（ CRF）.Methods A total of 60 Wistar rats were randomly divided into normal group,sham operation group,model group,low dose,middle dose and high dose of traditional Chinese medicine（ Guben Xiezhuo decoction） groups（ n = 10 for every group）,and 5 /6 nephrectomy was performed in other 5 groups to make CRF models except for normal group,while sham operation group underwent two times of operations in the same period without renal tissue resection. After 8 weeks of drug intervention,blood samples were obtained to detect levels of serum creatinine（ Scr）,urea nitrogen（ BUN） and hemoglobin（ HGB）,and immunohistochemistry method was used to detect TGF-β1 and BMP-9 expressions in nephridial tissues simultaneously,and then the mechanism of delaying renal failure of CRF rats was analyzed. Results Compared with those in normal group,Scr and BUN levels in other groups were all increased（ P〈0. 05）. Compared with those in sham operation group,Scr and BUN levels in model group and traditional Chinese medicine groups were all increased（ P〈0. 05）. Compared with those in model group,Scr and BUN levels in traditional Chinese medicine groups were decreased（ P〈0. 05）. BUN levels in high dose and middle dose of traditional Chinese medicine groups were lower than that in low dose group,and the level in high dose group was lower than that in middle dose group（ P〈0. 05）. Compared with those in normal and sham operation groups,HGB levels in other groups were decreased（ P〈0. 05）. Compared with that in model group,HGB levels in traditional Chinese medicine groups were increased（ P〈0. 05）. HGB levels in high dose and middle dose of traditional Chinese medicine groups were higher than that in low dose group,and the level in high dose group was higher than that in middle dose group（ P〈0. 05）. Compared with those in normal and sham operation groups,TGF-β1 grey values were decreased,while BMP-7 grey values were increased in other groups（ P〈0. 05）. Compared with those in model group,TGF-β1 grey values were increased,while BMP-7 gray values were decreased in traditional Chinese medicine groups（ P〈0. 05）. TGF-β1 grey values in high dose and middle dose of traditional Chinese medicine groups were higher,while BMP-7 gray values were lower than those in low dose group（ P〈0. 05）. TGF-β1gray value in high dose group was higher,while BMP-7 gray value was lower than that in middle dose group（ P〈0. 05）.Conclusion Guben Xiezhuo decoction can delay progress of renal interstitial fibrosis of rats with renal failure and improve renal function via down-regulating TGF-β1 protein expression and up-regulating BMP-7 protein expression.