Sophocarpine attenuates murine lupus nephritis via inhibiting NLRP3 inflammasome and NF-B activation
Sophocarpine attenuates murine lupus nephritis via inhibiting NLRP3 inflammasome and NF-B activation
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槐果碱通过抑制 NLRP3 炎性体和 NF-κB 激活减轻小鼠狼疮性肾炎
DOI：
10.1007/s12026-018-9012-9
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发表时间：
2018-08-01
影响因子：
4.4
通讯作者：
Yang, Ruiheng
中科院分区：
文献类型：
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作者：
Li, Xiuzhen;Wang, Mengjun;Yang, Ruiheng
狼疮性肾炎（lupus nephritis，LN）是系统性红斑狼疮（systemic lupus erythematosus，SLE）最严重的并发症，其发病机制与炎症有关。槐果碱是一种具有抗炎特性的喹里西啶生物碱。本研究探讨了槐果碱可能在LN中发挥有益作用的推测。雌性MRL/lpr小鼠接受槐果碱治疗8周。评价肾功能和组织病理学。通过免疫荧光染色测量免疫复合物沉积的水平，通过ELISA测量促炎细胞因子（IL-1、IL-6和TNF-α）和抗双链DNA（抗dsDNA）抗体的水平。Western blotting检测NLRP 3炎性小体和NF-B通路相关蛋白的表达水平。槐果碱治疗减少尿蛋白排泄，血尿素氮，减轻肾组织损伤。槐果碱能显著降低肾脏免疫复合物沉积、血清抗dsDNA抗体、血清和肾脏炎性细胞因子水平。槐果碱处理降低了形成NLRP 3炎性体的蛋白质的水平。槐果碱可抑制肾组织NF-B的活化。槐果碱能改善MRL/lpr实验性LN。这些作用可能是通过抑制NLRP 3炎性体和NF-B通路实现的。
Inflammation contributes to the pathogenesis of lupus nephritis (LN), which is the most serious complication that increases mortality of systemic lupus erythematosus (SLE). Sophocarpine is a type of quinolizidine alkaloid that possesses anti-inflammatory property. This study investigated the speculation that sophocarpine might play a beneficial effect in LN. Female MRL/lpr mice received sophocarpine treatment for 8weeks. Renal function and histopathology were evaluated. The level of immune complex deposition was measured by immunofluorescent staining, and the levels of proinflammatory cytokines (IL-1, IL-6, and TNF-) and anti-double-stranded DNA (anti-dsDNA) antibodies were measured by ELISA. Western blotting was carried out to evaluate the levels of proteins involved in NLRP3 inflammasome and NF-B pathway. Sophocarpine treatment reduced urine protein excretion, blood urea nitrogen, and attenuated renal tissue damage. The levels of renal immune complex deposition, serum anti-dsDNA, and serum and renal inflammatory cytokines were significantly reduced by sophocarpine. Sophocarpine treatment reduced the levels of proteins that form NLRP3 inflammasome. Activation of NF-B in the kidney was inhibited by sophocarpine. Sophocarpine could ameliorate experimental LN in MRL/lpr. These effects might be through suppressing NLRP3 inflammasome and NF-B pathway.