中文摘要：

我们以前报导了那 SM934，水溶性的 artemisinin 衍生物，是在鼠科的豺狼座模型的一个可行处理。在当前的学习，我们进一步在豺狼座容易的 MRL/lpr 老鼠上调查了 SM934 的修改剂量政体的治疗学的效果并且在 B 房间回答上探索了它的效果，在全身的豺狼座 erythematosus (SLE ) 的一个中央病原的事件。当口头上地管理了时两次每日， SM934 显著地延长了 MRL/lpr 老鼠的寿命，改善 lymphadenopathy 症状并且减少浆液的层次反原子的抗体(言论集) 并且病原的 cytokines IL-6， IL-10 和 IL-21。而且， SM934 处理由增加静止 B 房间数字在 MRL/lpr 老鼠的怒气恢复了 B 房间分隔空间，维持幼芽的中心 B 房间数字，减少激活的 B 房间数字和减少的血浆房间(PC ) 数字。前 vivo， SM934 压制了触发的像使用费的受体(TLR ) B 房间的激活和增长，以及抗体分泌物。而且，现在的学习证明 SM934 由 downregulating TLR7/9 mRNA 表示， MyD88 蛋白质表示和 NF-κ 防碍 B 房间内在的小径； B phosphorylation。在人的外部血 mononuclear 房间(PBMC ) ，与在 MRL/lpr 鼠标的结果一致， SM934 禁止了联系 TLR 的 B 房间激活和 PC 区别。在结论， SM934 的两次每日的 dosing 政体由压制 B 房间激活和血浆房间形成在豺狼座容易的 MRL/lpr 老鼠上有治疗学的效果。

英文摘要：

We previously reported that SM934, a water-soluble artemisinin derivative, was a viable treatment in murine lupus models. In the current study, we further investigated the therapeutic effects of a modified dosage regimen of SM934 on lupus-prone MRIJIpr mice and explored its effects on B cell responses, a central pathogenic event in systemic lupus erythematosus （SLE）. When orally administered twice-daily, SM934 significantly prolonged the life-span of MRL/Ipr mice, ameliorated the lymphadenopathy symptoms and decreased the levels of serum anti-nuclear antibodies （ANAs） and of the pathogenic cytokines IL-6, IL-10 and I L-21. Furthermore, SM934 treatment restored the B-cell compartment in the spleen of MRL/Ipr mice by increasing quiescent B cell numbers, maintaining germinal center B-cell numbers, decreasing activated B cell numbers and reducing plasma cell （PC） numbers. Ex vivo, SM934 suppressed the Toll-like receptor （TLR）-triggered activation and proliferation of B cells, as well as antibody secretion. Moreover, the present study demonstrated that SM934 interfered with the B-cell intrinsic pathway by downregulating TLR7/9 mRNA expression, MyD88 protein expression and NF-KB phosphorylation. In human peripheral blood mononuclear cells （PBMCs）, consistent with the results in MRIJIprmice, SM934 inhibited TLR-associated B-cell activation and PC differentiation. In conclusion, a twice daily dosing regimen of SM934 had therapeutic effects on lupus-prone MRL/Iprmice by suppressing B cell activation and plasma cell formation.