Triptolide reduces proteinuria in experimental membranous nephropathy and protects against C5b-9-induced podocyte injury in vitro
Triptolide reduces proteinuria in experimental membranous nephropathy and protects against C5b-9-induced podocyte injury in vitro
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DOI：
10.1038/ki.2010.41
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发表时间：
2010-06-01
影响因子：
19.6
通讯作者：
Liu, Zhi-Hong
中科院分区：
文献类型：
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作者：
Chen, Zhao-Hong;Qin, Wei-Song;Liu, Zhi-Hong
膜性肾病是成人肾病综合征的主要原因，足细胞损伤被发现介导蛋白尿的发展。雷公藤内酯醇是雷公藤的主要活性成分，具有较强的免疫抑制、抗炎和抗蛋白尿作用。为了研究其抗蛋白尿的作用，我们建立了大鼠被动性Heymann肾炎模型和体外足细胞C5 b-9损伤模型。雷公藤内酯醇治疗或预处理显着减少建立蛋白尿以及循环大鼠抗兔IgG抗体在这些肾炎大鼠的滴度，伴随着肾小球C5 b-9存款减少。足细胞损伤的标志物结蛋白的表达在雷公藤内酯醇治疗后减少，而平均足突宽度的定量分析表明足突的消失基本上被逆转。在体外研究中，我们发现雷公藤内酯醇使NADPH氧化酶失活，抑制活性氧的产生和p38丝裂原活化蛋白激酶，并恢复RhoA信号传导活性。雷公藤内酯醇不干扰足细胞膜上C5 b-9的形成。因此，雷公藤内酯醇减少被动Heymann肾炎大鼠中建立的重蛋白尿和足细胞损伤，并保护足细胞免受C5 b-9介导的损伤。Kidney International（2010）77，974-988; doi：10.1038/ki.2010.41; 2010年3月10日在线发表
Membranous nephropathy is a major cause of nephrotic syndrome in adults where podocyte injuries were found to mediate the development of proteinuria. Triptolide, a major active component of Tripterygium wilfordii Hook F, has potent immunosuppressive, anti-inflammatory and antiproteinuric effects. To study its antiproteinuric properties, we established an experimental rat model of passive Heymann nephritis and a C5b-9 injury model of podocytes in vitro. Treatment or pretreatment with triptolide markedly reduced established proteinuria as well as the titer of circulating rat anti-rabbit IgG antibodies in these nephritic rats, accompanied by a reduction in glomerular C5b-9 deposits. Expression of desmin, a marker of podocyte injury, diminished after triptolide treatment, whereas quantitative analysis of mean foot process width showed that effacement of foot processes was substantially reversed. In in vitro studies we found that triptolide deactivated NADPH oxidase, suppressed reactive oxygen species generation and p38 mitogen-activated protein kinase, and restored RhoA signaling activity. Triptolide did not interfere with the formation of C5b-9 on the membrane of podocytes. Thus, triptolide reduces established heavy proteinuria and podocyte injuries in rats with passive Heymann nephritis, and protects podocytes from C5b-9-mediated injury. Kidney International (2010) 77, 974-988; doi:10.1038/ki.2010.41; published online 10 March 2010