Polydatin effectively attenuates disease activity in lupus-prone mouse models by blocking ROS-mediated NET formation.
Polydatin effectively attenuates disease activity in lupus-prone mouse models by blocking ROS-mediated NET formation.
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虎杖甙通过阻断 ROS 介导的 NET 形成，有效减轻狼疮易发小鼠模型的疾病活动。
DOI：
10.1186/s13075-018-1749-y
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发表时间：
2018-11-12
影响因子：
4.9
通讯作者：
Sun E
中科院分区：
文献类型：
--
作者：
Liao P;He Y;Yang F;Luo G;Zhuang J;Zhai Z;Zhuang L;Lin Z;Zheng J;Sun E
中性粒细胞胞外陷阱（NET）的形成被认为与系统性红斑狼疮（SLE）的发病机制密切相关。在本研究中，我们旨在探讨虎杖苷（PD）对NET形成的影响以及其对易患狼疮小鼠模型疾病活动的作用。
在体外，用虎杖苷处理来自SLE患者和健康人的中性粒细胞，这些中性粒细胞分别用佛波醇12 - 肉豆蔻酸13 - 乙酸酯（PMA）或磷酸盐缓冲盐水（PBS）刺激，然后检测活性氧（ROS）的产生和NET的形成。在体内，用溶媒、虎杖苷、霉酚酸酯（MMF）或环磷酰胺（CYC）处理 pristane诱导的狼疮（PIL）小鼠，用溶媒或虎杖苷处理MRL/lpr小鼠。检测蛋白尿、血清自身抗体、活性氧产生、NET形成以及肾脏组织病理学情况。
与先前的研究结果一致，SLE患者血液中的中性粒细胞显示出自发性NET形成增加。在体内和体外，虎杖苷治疗均显著抑制中性粒细胞的活性氧产生和NET释放。在MRL/lpr小鼠模型中，虎杖苷给药降低了蛋白尿、循环自身抗体水平以及肾脏中NET和免疫复合物的沉积。此外，虎杖苷治疗改善了PIL小鼠的狼疮样特征，效果与MMF或CYC相同。
虎杖苷治疗抑制了活性氧介导的NET形成，并改善了PIL小鼠和MRL/lpr小鼠的狼疮症状。这些结果强调了NETosis在SLE发病机制中的作用，并揭示虎杖苷可能是SLE或其他自身免疫性疾病的一种潜在治疗药物。
BackgroundNeutrophil extracellular trap (NET) formation has been described to be closely involved in the pathogenesis of systemic lupus erythematosus (SLE). In this study, we aimed to investigate the effect of polydatin (PD) on NET formation and its effects on disease activity in lupus-prone mouse models.MethodsIn vitro, neutrophils from SLE patients and healthy people stimulated with phorbol 12-myristate 13-acetate (PMA) or phosphate-buffered saline (PBS) were treated with PD, and reactive oxygen species (ROS) production and NET formation examined. In vivo, pristane-induced lupus (PIL) mice were treated with vehicle, PD, mycophenolate mofetil (MMF) or cyclophosphamide (CYC) while MRL/lpr mice were treated with vehicle or PD. Proteinuria, serum autoantibodies, ROS production, NET formation and kidney histopathology were tested.ResultsConsistent with previous findings, blood neutrophils from SLE patients showed increased spontaneous NET formation. Both in vivo and in vitro, PD treatment significantly inhibited ROS production and NET release by neutrophils. In MRL/lprmouse model, PD administration reduced the proteinuria, circulating autoantibody levels, and deposition of NETs and immune complex in the kidneys. In addition, PD treatment ameliorated lupus-like features in PIL mice as MMF or CYC did.ConclusionsPD treatment inhibited ROS-mediated NET formation and ameliorated lupus manifestations in both PIL mice and MRL/lprmice. These results highlight the involvement of NETosis in SLE pathogenesis and reveal that PD might be a potential therapeutic agent for SLE or other autoimmune diseases.
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影响因子：
13.6
作者：
Crispín JC;Liossis SN;Kis-Toth K;Lieberman LA;Kyttaris VC;Juang YT;Tsokos GC
通讯作者：
Tsokos GC
影响因子：
--
作者：
Lai, Zhi-Wei;Hanczko, Robert;Bonilla, Eduardo;Caza, Tiffany N.;Clair, Brandon;Bartos, Adam;Miklossy, Gabriella;Jimah, John;Doherty, Edward;Tily, Hajra;Francis, Lisa;Garcia, Ricardo;Dawood, Maha;Yu, Jianghong;Ramos, Irene;Coman, Ioana;Faraone, Stephen V.;Phillips, Paul E.;Perl, Andras
通讯作者：
Perl, Andras
影响因子：
27.4
作者：
Knight JS;Subramanian V;O'Dell AA;Yalavarthi S;Zhao W;Smith CK;Hodgin JB;Thompson PR;Kaplan MJ
通讯作者：
Kaplan MJ
虎杖甙后处理可通过促进自噬通量减轻心肌缺血/再灌注损伤。
影响因子：
6
作者：
Ling, Yuanna;Chen, Guiming;Chen, Aihua
通讯作者：
Chen, Aihua
影响因子：
3.1
作者：
Du, Yong;Sanam, Soomro;Mohan, Chandra
通讯作者：
Mohan, Chandra