芪龙通肾方治疗膜性肾病大鼠蛋白尿的作用机制研究

Efficacy of Qilongtongshen Decoction for treatment of proteinuria in rats with membranous nephropathy:a mechanistic study

目的观察芪龙通肾方治疗膜性肾病大鼠蛋白尿的疗效及作用机制。方法将SD大鼠随机分为空白,模型,阳性(雷公藤多苷片),芪龙通肾汤低、中、高剂量组,采用隔日1次尾静脉注射阳离子化牛血清白蛋白(C-BSA)方法复制膜性肾病大鼠模型,各组连续腹腔内注射治疗4周后检测大鼠尿蛋白定量(24 h)及血清指标[总蛋白(TP)、白蛋白(ALB)、血清总胆固醇(TC)、甘油三酯(TG)、尿素氮(BUN)、肌酐(Scr)、转化生长因子(TGF)-β1],采用光镜及电镜观察肾脏病理学改变。结果与模型组比较:阳性及芪龙通肾汤低、中、高剂量组尿蛋白定量(24 h)明显降低(P<0.05),且芪龙通肾汤中、高剂量明显低于阳性组(P<0.05);阳性及芪龙通肾汤高剂量组对血清TP、TC明显降低(P<0.05);阳性、芪龙通肾汤低、中、高剂量组对血清ALB明显升高、对TG和TGF-β1明显降低(P<0.05)。光镜及电镜观察,治疗组在肾小球基底膜免疫复合物沉积、基底膜增厚及足突融合等方面较模型组明显减轻。结论芪龙通肾方能有效降低膜性肾病大鼠蛋白尿,提高血清白蛋白,降低TGF-β1水平,减轻肾脏病理损伤。

Objective To investigate the efficacy and mechanism of Qilongtongshen Decoction(QLTSD)for treatment of proteinuria in rats with membranous nephropathy.Methods SD rats were randomly divided into blank,model,active drug(tripterygium wilfordii polyglycoside tablets),low-,medium-and high-dose QLTSD groups.Membranous nephropathy in rats was modeled by caudal vein injection of cationized bovine serum albumin(C-BSA)once every other day.After 4 weeks of continuous intragastric gavage,the 24-hour urinary total protein(UTP)and serum biochemical parameters(TP,ALB,TC,TG,BUN,Scr,TGF-β1)were investigates in the rats.Light microscopy and electron microscopy were used to study the pathological changes of the kidney.Results The UTP in the active drug group,low-,medium-and high-dose QLTSD groups was significantly reduced compared with the model group(P<0.05),and was lower in the medium-and high-dose QLTSD groups compared with the active drug group(P<0.05).Compared with the model group,active drug and high-dose QLTSD led to significant reductions in serum TP and TC(P<0.05);active drug and all doses of QLTSD led to significant increase in serum ALB and reductions in serum TG and TGF-β1(P<0.05).Light microscopy and electron microscopy revealed that the treatment groups had significantly milder in immune complex deposition,thickening and fusion of podocyte foot processes at glomerular basement membrane,compared with the model group.Conclusion Qilongtongshen Decoction can effectively relieve proteinuria,increase serum albumin,reduce the TGF-β1 level,and ameliorate renal pathological lesions in rats with membranous nephropathy.