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3-乙酰氧基齐墩果酸通过调节 Th17 分化来减轻马兜铃酸诱导的狼疮肾炎。

3-Acetyloxy-oleanolic Acid Attenuates Pristane-Induced Lupus Nephritis by Regulating Th17 Differentiation.

机构信息

Institute of Human Virology, Sun Yat-Sen University, Guangzhou, China.

Department of Biochemistry and Molecular Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.

出版信息

J Immunol Res. 2019 May 22;2019:2431617. doi: 10.1155/2019/2431617. eCollection 2019.

Abstract

Th17 activity has been implicated in systemic lupus erythematosus (SLE), which is a systemic autoimmune disease with a typical clinical manifestation of lupus nephritis (LN). Retinoic acid receptor-related orphan receptor gamma t (RORt) has been shown to be important for Th17 differentiation. In this study, we evaluated the inhibition of RORt activity by 3-acetyloxy-oleanolic acid (AOA), a small molecule isolated from the root of , a traditional herb belonging to South China. We demonstrated that AOA can inhibit RORt activity and prevent SLE pathogenesis in a pristane-induced LN model. The results showed that AOA decreased RORt transcription activity in a reporter assay and prevented Th17 differentiation . studies showed that AOA treatment decreased serum anti-dsDNA antibody and alleviated renal pathologic damage as well as antibody complex accumulation in the pristane-induced LN model. These results demonstrated that AOA can improve the clinical manifestation of LN, indicating potential application in SLE therapy.

摘要

Th17 活性与系统性红斑狼疮(SLE)有关,SLE 是一种系统性自身免疫性疾病,其典型临床表现为狼疮肾炎(LN)。维甲酸受体相关孤儿受体γ t(RORγ t)对于 Th17 分化非常重要。在这项研究中,我们评估了从 根部分离得到的小分子 3-乙酰氧基齐墩果酸(AOA)对 RORγ t 活性的抑制作用, 是华南地区的一种传统草药。我们证明 AOA 可以抑制 RORγ t 活性,并预防经正十六烷诱导的 LN 模型中的 SLE 发病机制。结果表明,AOA 在报告基因检测中降低了 RORγ t 的转录活性,并阻止了 Th17 分化。 研究表明,AOA 治疗降低了血清抗 dsDNA 抗体,并减轻了正十六烷诱导的 LN 模型中的肾脏病理损伤和抗体复合物积聚。这些结果表明 AOA 可以改善 LN 的临床表现,表明其在 SLE 治疗中有潜在的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b002/6556267/a736a637e79f/JIR2019-2431617.001.jpg

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