雷公藤甲素对嘌呤霉素模型足细胞病变的影响  

Therapeutic effect of triptolide on podocyte injury in nephrosis rats induced by puromycin aminonucleoside

作　　者：郑春霞[1] 刘志红[1] 孙吉平[1] 曾彩虹[1] 王生余[1] 黎磊石[1] 

机构地区：[1]南京军区南京总医院解放军肾脏病研究所,南京210002

出　　处：《肾脏病与透析肾移植杂志》2007年第2期110-118,共9页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：全军"十一五"重点课题(06G040);南京军区"十一五"重点课题(06235)

摘　　要：目的:研究雷公藤甲素对非免疫因素介导的、单纯足细胞病变模型——嘌呤霉素氨基核苷(PAN)肾病模型的疗效及其对足细胞病变的影响。方法:采用PAN单次颈静脉注射法建立PAN肾病模型。大鼠分为正常对照组,模型组,雷公藤甲素预防组和治疗组。分别在1天、3天、5天、10天、14天和21天收集血尿标本,并处死大鼠留取肾组织标本。检测24h尿蛋白排泄量、血生化指标,行肾组织光镜和电镜观察肾小球病变和足突超微结构。采用定量学方法测定足突宽度。免疫荧光染色观察足细胞裂孔膜分子Nephrin和Podocin表达和分布变化。结果:雷公藤甲素无论是预防还是治疗性用药均能明显改善PAN肾病大鼠的肾病综合征状况,明显减少尿蛋白,加快血清白蛋白回升和血脂水平恢复。与此同时,雷公藤甲素预防组和治疗组大鼠在各观察点足突融合程度和范围均比PAN肾病大鼠明显减轻,至第14天仅见少数足突融合,第21天足突形态已基本恢复正常。雷公藤甲素预防性和治疗性用药均能够增加足细胞裂孔膜分子Nephrin和Podocin表达,促进其分布异常的修复。在第10天,Nephrin和Podocin不仅表达较PAN肾病大鼠明显增多,而且大部分血管袢已开始呈现连续的线状分布,以Podocin更为明显;两者的表达和分布在第14天已基本恢复,至第21天已完全恢复正常。结论:雷公藤甲素对PAN导致的足细胞损伤模型具有明显的预防和治疗作用,表现为减少蛋白尿,改善足突融合,恢复足细胞相关蛋白的表达及其分布,逆转足细胞病变。Objective：To investigate the preventive and therapeutic effect of triptolide on puromycin aminonucleoside （PAN）-induced （nonimmune-mediated） nephrosis rats and its effect on podocyte injuries. Methodology：An animal model of nephrosis induced by PAN was established by single intravenous injection of PAN. These SD rats were divided randomly into normal control, PAN nephrosis control, triptolide-preventative group and triptolide-therapeutic group. At each time point, the blood and urine samples were collected, and renal tissues were processed after killed. The 24h urinary protein excretion and blood biochemistry parameters were measured by routine methods. The glomerular morphology and podocyte uhrastructure were observed by light microscopy and transmission electron microscopy respectively. The foot process width was examind by morphometric method. The nephrin and podocin expression and distribution change were determined by indirect immunofluorescence staining. Results. In both of triptolide-preventative and therapeutic groups, the nephrotic syndrome of PAN rats was significantly improved compared with that in PAN nephrosis control. Their urinary protein excretion was decreased, plasma albumin was increased, and high cholesterol/triglyceride levels were remission. Meanwhile, the degree and area of podocte processes effacement was significantly reduced in both of triptolide-preventative and therapeutic groups. A minor of podocte processes effacement was left on 14^th day, and podocyte processes morphology was restored to normal on 21^st day. The expression and distribution of nephrin and pedocin was also significantly improved by triptolide. On the 10^th day, compared with that in PAN nephrosis control, not only the expression of nephrin and pedocin increased, but also the distribution of them appeared to be continuous linear. The expression and distribution of nephrin and podocin almost recovered on 14^th day and completely restored to normal on 21^st, day in both of triptolide-preventative and therape

关 键 词：雷公藤甲素 嘌呤霉素氨基核苷 蛋白尿 足细胞 NEPHRIN PODOCIN 

分 类 号：R285.5[医药卫生—中药学]