Artemisinin analogue SM934 protects against lupus-associated antiphospholipid syndrome via activation of Nrf2 and its targets
Artemisinin analogue SM934 protects against lupus-associated antiphospholipid syndrome via activation of Nrf2 and its targets
复制标题
青蒿素类似物 SM934 通过激活 Nrf2 及其靶标来预防狼疮相关的抗磷脂综合征。
DOI：
10.1007/s11427-020-1840-1
复制
发表时间：
2021-01-19
影响因子：
9.1
通讯作者：
Zuo, Jianping
中科院分区：
文献类型：
--
作者：
Lin, Zemin;Liu, Yuting;Zuo, Jianping
肾脏是抗磷脂综合征（APS）和系统性红斑狼疮（SLE）的主要靶器官。抗磷脂综合征肾病相关狼疮性肾炎（APSN-LN）的病因是复杂的，仍然在很大程度上未被发现。我们在目前的工作中提出，抗磷脂抗体（aPL）的产生，特别是那些针对氧化的新表位，在很大程度上与氧化还原状态沿着疾病的进展。此外，我们观察到，受损的抗氧化能力与患有APSN-LN的雄性NZWxBXSB F1小鼠肾脏中炎性细胞因子谱的紊乱一致。SM 934是一种青蒿素衍生物，已被证明具有有效的免疫抑制特性。在目前的研究中，我们首次阐述了SM 934在雄性NZWxBXSB F1小鼠中的治疗益处，该小鼠模型首次出现与SLE相关的类似人类APS的综合征。SM 934治疗全面阻止了肾脏中自身抗体的产生、炎性细胞因子的积累和过度的氧化应激。其中，我们在目前的工作中解释了SM 934的抗炎和抗氧化作用与Nrf 2信号转导及其靶点表达的增强密切相关。总的来说，我们的发现证实，同时发挥抗氧化和抗炎功效的治疗策略为治疗APSN-LN提供了一种新的可行疗法。
Kidney is a major target organ in both antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). The etiology of antiphospholipid syndrome nephropathy associated lupus nephritis (APSN-LN) is intricate and remains largely unrevealed. We proposed in present work, that generation of antiphospholipid antibodies (aPLs), especially those directed towards the oxidized neoepitopes, are largely linked with the redox status along with disease progression. Moreover, we observed that compromised antioxidative capacity coincided with turbulence of inflammatory cytokine profile in the kidney of male NZWxBXSB F1 mice suffered from APSN-LN. SM934 is an artemisinin derivative that has been proved to have potent immunosuppressive properties. In current study, we elaborated the therapeutic benefits of SM934 in male NZWxBXSB F1 mice, a murine model develops syndrome resembled human APS associated with SLE, for the first time. SM934 treatment comprehensively impeded autoantibodies production, inflammatory cytokine accumulation and excessive oxidative stress in kidney. Among others, we interpreted in present work that both anti-inflammatory and antioxidative effects of SM934 is closely correlated with the enhancement of Nrf2 signaling and expression of its targets. Collectively, our finding confirmed that therapeutic strategy simultaneously exerting antioxidant and anti-inflammatory efficacy provide a novel feasible remedy for treating APSN-LN.