Imperatorin alleviated NLR family pyrin domain-containing 3 inflammasome cascade-induced synovial fibrosis and synovitis in rats with knee osteoarthritis.

Imperatorin alleviated NLR family pyrin domain-containing 3 inflammasome cascade-induced synovial fibrosis and synovitis in rats with knee osteoarthritis.
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欧前胡素减轻 NLR 家族吡啶结构域 3 炎症小体级联诱导的膝骨关节炎大鼠滑膜纤维化和滑膜炎

DOI:
10.1080/21655979.2021.2012949
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发表时间:
2021-12
期刊:
影响因子:
4.9
通讯作者:
Wang P
Wang P
中科院分区:
生物学2区
文献类型:
--
作者:
Zhang H;Ding L;Shi X;Mei W;Huang Z;Zhang L;Li X;Xu B;Zhang L;Wang P

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摘要我们旨在阐明欧前胡素(IMP)对膝骨关节炎(KOA)的治疗作用。30只3月龄SD雄性大鼠随机分为正常组、碘乙酸钠(MIA)组和MIA+IMP组。滑膜组织进行组织病理学分析。另取正常大鼠滑膜成纤维细胞,经脂多糖(LPS)和IMP处理后,分别采用qRT-PCR和Western blotting检测滑膜炎和滑膜纤维化相关因子mRNA和蛋白的表达。ELISA法检测血清IL-1β、IL-18水平。IMP可减少脂多糖诱导的滑膜成纤维细胞中HIF-1α、NLR家族pyrin结构域3炎性体的表达以及IL-1β、IL-18的产生。IMP还下调滑膜纤维化标志物。体外研究显示IMP可减轻MIA诱导的滑膜炎和滑膜纤维化。IMP可减轻与滑膜炎和滑膜纤维化相关的炎症。它减少促炎介质和细胞因子的产生,并抑制促进滑膜纤维化的TGF-β1、TIMP-1和VEGF表达。
ABSTRACT We aimed to clarify the therapeutic effects of imperatorin (IMP) on knee osteoarthritis (KOA). Thirty 3-month-old SD male rats were randomly divided into Normal, monosodium iodoacetate (MIA) and MIA+IMP groups. Their synovial tissues were subjected to histopathological analysis. Primary synovial fibroblasts obtained from additional normal rats were treated by lipopolysaccharide (LPS) and then IMP. The mRNA and protein expressions of factors related to synovitis and synovial fibrosis were detected by qRT-PCR and Western blotting, respectively. The concentrations of inflammatory factors IL-1β and IL-18 were measured by ELISA. IMP reduced HIF-1α, NLR family pyrin domain-containing 3 inflammasome expression and IL-1β, IL-18 production in synovial fibroblasts induced by LPS. IMP also downregulated synovial fibrosis markers. In vitro study revealed that MIA-induced synovitis and synovial fibrosis were relieved by IMP. IMP relieves the inflammation associated with synovitis and synovial fibrosis. It reduces the production of pro-inflammatory mediators and cytokines and inhibits TGF-β1, TIMP-1 and VEGF expressions that promote synovial fibrosis.
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发表时间: 2020-06-01
期刊: KNEE
影响因子: 1.9
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