芪地固肾方对膜性肾病大鼠肾组织足细胞裂孔隔膜蛋白Nephrin和Podocin表达的影响

Effects of Qidi Gushen Recipe on the Expression of Podocyte Hiatus Membrane Proteins Nephrin and Podocin in Renal Tissue of Rats with Membranous Nephropathy

目的:探讨芪地固肾方治疗膜性肾病(MN)大鼠的效果及其可能的机制。方法:将40只SD雄性大鼠随机分为模型组(等剂量生理盐水尾静脉注射)、雷公藤多甙片组(10 mg/kg雷公藤多甙片)、芪地固肾方低剂量组(15.425 g/kg芪地固肾方)、芪地固肾方高剂量组(61.7 g/kg芪地固肾方)四组,另取10只未造模大鼠作为空白组(等剂量生理盐水尾静脉注射),连续干预28天后,检测24小时尿蛋白定量(U-TP)、血清总蛋白(TP)、白蛋白(ALB)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、血肌酐(Scr)、尿素氮(BUN)的变化;HE染色、透射电镜观察大鼠肾组织病理学改变;RT-PCR检测肾组织中nephrin蛋白、podocin m RNA的表达。结果:与空白组比较,模型组24 hU-TP、足细胞nephrin和podocin m RNA显著升高,血清TP和ALB显著降低(P<0.01);与模型组比较,各给药组24 hU-TP降低,血清TP和ALB显著升高(P<0.05);肾组织免疫复合物沉积减少,肾小球基底膜增厚减轻;足细胞nephrin和podocin m RNA表达升高(P<0.05)。结论:芪地固肾方能够降低MN模型大鼠的尿蛋白水平,减轻肾脏病理损伤,上调肾组织中足细胞裂孔隔膜蛋白nephrin和podocin m RNA的表达,延缓膜性肾病的进展。

Objective: To investigate the effect and possible mechanism of Qidi Gushen recipe in the treatment of MN rats. Methods: Forty SD male rats were randomly divided into model group(with equal dose of normal saline tail vein injection), tripterygium glycosides group(10 mg/kg tripterygium glycosides), the low-dose group of Qidi Gushen recipe(15.425 g/kg of Qidi Gushen recipe) and the high-dose group of Qidi Gushen recipe(61.7 g/kg of Qidi Gushen recipe). Another 10 unmodeled rats were taken as the blank group(the same dose of normal saline was injected into the tail vein), and after continuous intervention for 28 days, the changes of 24-hour U-TP,TP, ALB, ALT, AST, Scr, BUN were detected;The pathological changes of rat kidney tissue were observed by HE staining and transmission electron microscope;the expression of nephrin protein and podocin m RNA in renal tissue was detected by RT-PCR. Results: Compared with the blank group, 24 hU-TP, podocyte nephrin and podocin m RNA of the model group were significantly increased, while serum TP and ALB were significantly decreased(P<0.01);compared with the model group, the 24 hU-TP of each administration group decreased, and the serum TP and ALB significantly increased(P<0.05), the renal tissue immune complex deposition decreased, and the glomerular basement membrane was thickened, the expression of nephrin and podocin m RNA in podocytes increased(P<0.05). Conclusions: Qidi Gushen Decoction can reduce the level of urine protein in MN model rats, reduce pathological damage of kidney, up-regulate the expression of podocyte split membrane protein nephrin and podocin m RNA in renal tissue, and delay the progression of membranous nephropathy.