Zheng Chun-Xia, Chen Zhao-Hong, Zeng Cai-Hong, Qin Wei-Song, Li Lei-Shi, Liu Zhi-Hong
Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Kidney Int. 2008 Sep;74(5):596-612. doi: 10.1038/ki.2008.203. Epub 2008 May 28.
Extracts of Tripterygium wilfordii Hook F have been used to treat glomerulonephritis for more than 30 years in China with dramatic antiproteinuric effects. Triptolide, a diterpene triepoxide, is one of the major active components of these extracts. To clarify its antiproteinuric effects we induced podocyte injury by puromycin aminonucleoside. Triptolide effectively reduced the proteinuria induced by puromycin in nephrotic rats without reducing the glomerular filtration rate. The antiproteinuric effect was associated with improvement in the foot process effacement, a decrease in the podocyte injury marker desmin as well as the restoration of nephrin and podocin expression and distribution. In cultured mouse podocytes triptolide pretreatment prevented the puromycin-induced disruption of the actin cytoskeleton and microfilament-associated synaptopodin while protecting nephrin and podocin expression. Triptolide suppressed reactive oxygen species generation and p38 mitogen-activated protein kinase activation while restoring RhoA signaling activity. These results show that triptolide ameliorates puromycin aminonucleoside-mediated podocyte injury in vivo and in vitro.
在中国，雷公藤提取物用于治疗肾小球肾炎已有30多年，具有显著的抗蛋白尿作用。雷公藤内酯醇是一种二萜三环氧物，是这些提取物的主要活性成分之一。为阐明其抗蛋白尿作用，我们用嘌呤霉素氨基核苷诱导足细胞损伤。雷公藤内酯醇可有效降低嘌呤霉素诱导的肾病大鼠蛋白尿，而不降低肾小球滤过率。其抗蛋白尿作用与足突消失改善、足细胞损伤标志物结蛋白减少以及nephrin和podocin表达及分布恢复有关。在培养的小鼠足细胞中，雷公藤内酯醇预处理可防止嘌呤霉素诱导的肌动蛋白细胞骨架和微丝相关的突触素破坏，同时保护nephrin和podocin表达。雷公藤内酯醇抑制活性氧生成和p38丝裂原活化蛋白激酶激活，同时恢复RhoA信号活性。这些结果表明，雷公藤内酯醇在体内和体外均可改善嘌呤霉素氨基核苷介导的足细胞损伤。
