雷公藤甲素对嘌呤霉素模型足细胞病变的影响

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。

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

Objective: To investigate the preventive and therapeutic effect of triptolide on puromycin aminonucleoside (PAN)-induced (nonimmune-mediated) nephrosis rats and its effe ct on podocyte injuries. Methodology: An animal model of nephrosis induced by PAN was established by single intravenou s injection of PAN. These SD rats were divided randomly into normal control, PAN nephrosis control, triptolide-preventative group and triptolide-therapeutic g roup. 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 morpho logy and podocyte ultrastructure were observed by light microscopy and transmiss ion electron microscopy respectively. The foot process width was examind by morp hometric 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 syndro me of PAN rats was significantly improved compared with that in PAN nephrosis co ntrol. Their urinary protein excretion was decreased, plasma albumin was increas ed, and high cholesterol/triglyceride levels were remission. Meanwhile, the degr ee and area of podocte processes effacement was significantly reduced in both of triptolide-preventative and therapeutic groups. A minor of podocte processes e ffacement was left on 14th day, and podocyte processes morphology was rest ored to normal on 21st day. The expression and distribution of nephrin and podocin was also significantly improved by triptolide. On the 10th day, c ompared with that in PAN nephrosis control, not only the expression of nephrin a nd podocin increased, but also the distribution of them appeared to be continuou s linear. The expression and distribution of nephrin and podocin almost recovere d on 14th day and completely restored to normal on 21st day in both of triptolide-preventative and therapeutic group. Conclusion: Triptolide has significant preventive and therapeutic effect on PAN-induced pod ocyte injury model. The effects represent the reducing proteinuria, improving po docyte processes effacement, recovering podocye associated protein expression an d distribution, and reversing podocyte injury in nephrosis rats induced by PAN.