Vanillic Acid Reduces Pain-Related Behavior in Knee Osteoarthritis Rats Through the Inhibition of NLRP3 Inflammasome-Related Synovitis.
Vanillic Acid Reduces Pain-Related Behavior in Knee Osteoarthritis Rats Through the Inhibition of NLRP3 Inflammasome-Related Synovitis.
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香草酸通过抑制 NLRP3 炎症小体相关滑膜炎减少膝骨关节炎大鼠的疼痛相关行为
DOI：
10.3389/fphar.2020.599022
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发表时间：
2020
影响因子：
5.6
通讯作者：
Wang P
中科院分区：
文献类型：
--
作者：
Ma Z;Huang Z;Zhang L;Li X;Xu B;Xiao Y;Shi X;Zhang H;Liao T;Wang P
目的：滑膜炎在膝关节骨关节炎（KOA）疼痛中起重要作用。成纤维细胞样滑膜细胞（FLSs）中nod样受体蛋白3 （NLRP3）炎性体的激活促进KOA的发展。在这项研究中，我们旨在研究香草酸（VA），一种源自中草药的单体，是否可以靶向NLRP3炎症小体相关滑膜炎以减轻疼痛。方法：KOA组和KOA + VA组大鼠膝关节注射碘乙酸单钠（MIA）诱导KOA。从第14天开始，KOA + VA组通过胃插管给予VA 30 mg/kg / d。从滑膜组织中收集FLSs。我们在体内和体外检测了caspase-1、带有caspase募集结构域（ASC）的凋亡相关斑点样蛋白、NLRP3、NLRP3炎性体组分、白细胞介素-1β (IL-1β)和IL-18的蛋白和基因表达。结果：VA可降低KOA模型中caspase-1、ASC、NLRP3的上调，同时降低KOA模型中IL-1β、IL-18的水平。此外，VA还能缓解KOA模型大鼠的疼痛相关行为，下调fls中疼痛介质CGRP、NGF和TrkA的表达。有趣的是，我们在动物实验中也观察到滑膜纤维化减少。结论：我们的研究表明，VA可减轻KOA大鼠滑膜炎和疼痛相关行为，为进一步研究VA对KOA的潜在治疗作用提供了基础。
Objectives: Synovitis plays an important role in knee osteoarthritis (KOA) pain. The activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in fibroblast-like synoviocytes (FLSs) promotes KOA development. In this study, we aimed to investigate whether vanillic acid (VA), a monomer derived from Chinese herbal medicines, could target NLRP3 inflammasome-related synovitis to reduce pain. Methods: Rats in the KOA and KOA + VA groups were injected with monosodium iodoacetate (MIA) in the knee to induce KOA. From day 14, the KOA + VA group was given VA at 30 mg/kg every day via gastric intubation. FLSs were collected from the synovial tissues. We examined both the protein and gene expression of caspase-1, apoptosis-associated speck-like protein with a caspase recruitment domain (ASC), NLRP3, components of the NLRP3 inflammasome, and interleukin-1β (IL-1β) and IL-18 in vivo and in vitro. Results: The upregulation of caspase-1, ASC, and NLRP3 in the KOA model were reduced by VA. VA also lowered the level of IL-1β and IL-18 in the KOA model. In addition, VA relieved pain-related behavior of KOA model rats and downregulated the pain mediators CGRP, NGF, and TrkA in FLSs. Interestingly, we also observed reduced synovial fibrosis in the animal experiments. Conclusion: Our research showed that VA reduces synovitis and pain-related behaviors in a rat model of KOA, which provides the basis for further investigations into the potential therapeutic impact of VA in KOA.
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影响因子：
2.7
作者：
Takano S;Uchida K;Inoue G;Minatani A;Miyagi M;Aikawa J;Iwase D;Onuma K;Mukai M;Takaso M
通讯作者：
Takaso M
影响因子：
4.9
作者：
Pecchi E;Priam S;Gosset M;Pigenet A;Sudre L;Laiguillon MC;Berenbaum F;Houard X
通讯作者：
Houard X
影响因子：
16
作者：
Martinon, F;Burns, K;Tschopp, J
通讯作者：
Tschopp, J
香草酸通过调节 MAPK 和 PI3K/AKT/NF-kappa B 通路减轻软骨退化
影响因子：
5
作者：
Huang, Xiaojian;Xi, Yang;You, Hongbo
通讯作者：
You, Hongbo
DOI：
10.1038/s41584-019-0266-y
发表时间：
2019-08-01
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
Collison, Joanna
通讯作者：
Collison, Joanna