固本泄浊饮延缓5/6肾切除大鼠慢性肾功能衰竭的机制研究

目的 研究固本泄浊饮延缓5/6肾切除大鼠慢性肾功能衰竭(chronic renal failure,CRF)的作用机制.方法 60只雄性Wistar大鼠分为假手术组、模型组、氯沙坦钾组与中药(固本泄浊饮)高、中、低剂量组,每组10只,给药后4、8周检测各组大鼠血肌酐(serum creatinine,Scr)和24 h尿蛋白水平,同时给药后8周分别通过HE染色法、免疫组化法检测各组大鼠残肾组织病理变化及肾组织转化生子因子-β1(transfonning growth factor-β1,TGF-β1)、结缔组织生长因子(connective tissue growth factor,CTGF)、重组人血小板源性生长因子-BB(platelet derived growth factor-BB,PDGF-BB)表达情况.结果 与假手术组比较,模型组、氯沙坦钾组、中药高、中、低剂量组给药4、8周血清Scr、24 h尿蛋白、TGF-β1、CTGF、PDGF-BB表达均不同程度增高(P＜0.05);与模型组比较,氯沙坦钾组、中药高、中、低剂量组给药4、8周血清Scr、24 h尿蛋白、TGF-β1、CTGF、PDGF-BB表达降低,且中药高、中剂量组上述指标均明显低于氯沙坦钾组(P＜0.05).光镜显示假手术组大鼠肾小球、肾小管正常,肾间质基本无纤维化;模型组大部分肾小球体积减小,肾间质出现一定程度的纤维化;氯沙坦钾组及中药组治疗8周后显示肾小球硬化程度、肾纤维化程度减轻.结论 固本泄浊饮能有效延缓5/6肾切除大鼠CRF进展,其作用机制可能与其降低血清Scr和24 h尿蛋白,抑制肾脏TGF-β1、CTGF、PDGF-BB等表达有关.

A Study on Mechanism of Guben Xiezhuo Decoction in Delaying Progress of Chronic Renal Failure in Rats with 5/6 Nephrectomy

Objective To investigate mechanism of Guben Xiezhuo Decoction in delaying progress of chronic renal failure (CRF) in rats with 5/6 nephrectomy.Methods A total of 60 Wistar rats were randomly divided into sham operation group,model group,Losartan group and high,medium and low dose,middle dose and high dose of traditional Chinese medicine (Guben Xiezhuo decoction) groups (n =10 for each group).Levels of serum creatinine (Scr) and 24 h urine protein were detected after administration for 4 and 8 weeks.Meanwhile,pathological changes of remnant renal tissues and expressions of transforming growth factor-β1 (TGF-β1),connective tissue growth factor (CTGF) and platelet derived growth factor-BB (PDGF-BB) were detected after administration for 8 weeks.Results Compared with those in sham operation group,serum Scr and 24h urinary protein levels,and TGF-β1,CTGF and PDGF-BB expressions after administration for 4 and 8 weeks in model group,Losartan group,low dose,middle dose and high dose of traditional Chinese medicine groups were significantly higher (P ＜ 0.05).Compared with those in model group,serum Scr and 24h urinary protein levels,and TGF-β1,CTGF and PDGF-BB expressions after administration for 4 and 8 weeks in Losartan group,low dose,middle dose and high dose of traditional Chinese medicine groups were significantly lower,and the above indexes middle dose and high dose of traditional Chinese medicine groups were significantly lower than those in Losartan group (P ＜ 0.05).Light microscopy showed that the glomeruli and kidney tubules were normal without fibrosis in renal interstitium in sham operation group;in model group,volumes of most of glomeruli were decreased,and there was a certain degree of fibrosis in renal interstitium;glomerular sclerosis and renal fibrosis were relieved in Losartan and traditional Chinese medicine groups after 8 weeks of treatment.Conclusion Guben Xiezhuo Decoction can effectively delay the progress of chronic renal failure in rats with 5/6 nephrectomy,and its mechanism may be related to decreasing serum Scr and 24 h urinary protein levels,and inhibiting TGF-β1,CTGF and PDGF-BB expressions.