Effective therapy for nephritis in (NZB x NZW)F1 mice with triptolide and tripdiolide, the principal active components of the Chinese herbal remedy Tripterygium wilfordii Hook F
Effective therapy for nephritis in (NZB x NZW)F1 mice with triptolide and tripdiolide, the principal active components of the Chinese herbal remedy Tripterygium wilfordii Hook F
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DOI：
10.1002/art.23513
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发表时间：
2008-06-01
影响因子：
--
通讯作者：
Lipsky, Peter E.
中科院分区：
文献类型：
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作者：
Tao, Xuelian;Fan, Fred;Lipsky, Peter E.
客观的。雷公藤甲素和雷公藤内酯被认为是中药雷公藤甲素雷公藤甲素的活性成分，已被证明可有效治疗小鼠狼疮性肾炎。本研究旨在检验雷公藤甲内酯和雷公藤甲内酯对 (NZB X NZW)F-1 小鼠狼疮性肾炎的治疗效果。方法。 (NZB x NZW)F-1 mice were treated with vehicle, triptolide, or tripdiolide for 15 weeks beginning at the age of 29 weeks (after the development of lupus nephritis).监测体重、蛋白尿和抗双链DNA（抗dsDNA）抗体，并对肾脏和脾脏进行组织学评估。检测脾单核细胞培养上清液中的细胞因子。结果。到 28 周时，大多数 (NZB X NZW)F-1 小鼠患上了狼疮肾炎。载体治疗的小鼠表现出进行性蛋白尿、低蛋白血症、血尿素氮（BUN）水平升高以及严重肾炎的证据。相反，与用媒介物治疗的小鼠相比，用雷公藤甲内酯或雷公藤内酯治疗的小鼠的蛋白尿和BUN水平显着降低。用这两种二萜类化合物治疗的小鼠没有出现低白蛋白血症或狼疮性肾炎的明显证据。 44 周龄时，用媒介物治疗的小鼠的存活率 (35.7%) 显着低于用雷公藤甲内酯 (87.5%) 或雷公藤内酯 (88.2%) 治疗的小鼠。治疗过程完成后，用雷公藤内酯治疗的小鼠中抗 dsDNA 抗体的平均水平低于用媒介物治疗的小鼠中的平均水平。二萜类药物治疗后，脾细胞产生的肿瘤坏死因子、白细胞介素 6 和单核细胞趋化蛋白 1 也减少。结论。雷公藤甲内酯或雷公藤内酯治疗可显着改善 (NZB X NZW)F-1 小鼠的狼疮性肾炎，减少细胞因子和趋化因子的产生，并延长生存期。
Objective. Triptolide and tripdiolide are thought to be active components of the Chinese antirheumatic herbal remedy Tripterygium wilfordii Hook F, which has been shown to be effective in treating murine lupus nephritis. This study was undertaken to examine the therapeutic effect of triptolide and tripdiolide on established lupus nephritis in (NZB X NZW)F-1 mice.Methods. (NZB x NZW)F-1 mice were treated with vehicle, triptolide, or tripdiolide for 15 weeks beginning at the age of 29 weeks (after the development of lupus nephritis). Body weight, proteinuria, and anti-double-stranded DNA (anti-dsDNA) antibodies were monitored, and the kidney and spleen were assessed histologically. Culture supernatants of spleen mononuclear cells were assayed for cytokines.Results. By 28 weeks, most (NZB X NZW)F-1 mice had developed lupus nephritis. Vehicle-treated mice exhibited progressive proteinuria, hypoalbuminemia, elevated blood urea nitrogen (BUN) levels, and evidence of severe nephritis. In contrast, proteinuria and BUN levels were significantly reduced in mice treated with either triptolide or tripdiolide as compared with those treated with vehicle. There was no hypoalbuminemia or apparent evidence of lupus nephritis in mice treated with either of the 2 diterpenoids. At 44 weeks of age, the survival rate in mice treated with vehicle (35.7%) was markedly lower than that in mice treated with either triptolide (87.5%) or tripdiolide (88.2%). The mean level of anti-dsDNA antibody in mice treated with tripdiolide was lower than that in the vehicle-treated mice upon completion of the treatment course. Production of tumor necrosis factor, interleukin-6, and monocyte chemoattractant protein 1 by spleen cells was also decreased after diterpenoid therapy.Conclusion. Therapy with triptolide or tripdiolide significantly ameliorated lupus nephritis in (NZB X NZW)F-1 mice, reduced cytokine and chemokine production, and prolonged survival.