苏萸痛风方通过ROS/TXNIP/NLRP3信号通路抗痛风性关节炎的作用机制
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篇名: 苏萸痛风方通过ROS/TXNIP/NLRP3信号通路抗痛风性关节炎的作用机制
TITLE: Mechanism of Suyu tongfeng prescription in the treatment of gouty arthritis through ROS/TXNIP/NLRP 3 signaling pathway
摘要: 目的 研究苏萸痛风方抗痛风性关节炎的作用机制。方法将雄性SD大鼠按体质量随机分为正常对照组、模型组、秋水仙碱片组(阳性对照药,0.3mg/kg)和苏萸痛风方高、中、低剂量组(5、2.5、1.25g/kg),每组10只。给药组大鼠每日灌胃相应药物1次(10mL/kg),连续给药7d。正常对照组和模型组大鼠同法灌胃等体积水。第6天给药后1h,除正常对照组外,其余各组大鼠于关节腔注入尿酸钠复制痛风性关节炎模型。检测大鼠造模后2、6、24h的关节肿胀度和炎症指数评分。末次给药后1h,检测大鼠血清中氧化应激相关指标[超氧化物歧化酶(SOD)、黄嘌呤氧化酶(XOD)、丙二醛(MDA)]活性及炎症因子[白细胞介素1β(IL-1β)、IL-18、肿瘤坏死因子α(TNF-α)]水平,观察各组大鼠踝关节组织病理学变化,检测大鼠踝关节组织中硫氧还蛋白互作蛋白(TXNIP)、NOD样受体热蛋白结构域相关蛋白3(NLRP3)、凋亡相关斑点样蛋白(ASC)的表达水平。结果经苏萸痛风方干预后,大鼠关节肿胀度减轻、炎症指数评分降低、滑膜组织水肿改善、炎症细胞数量减少。苏萸痛风方高剂量组大鼠血清中SOD活性显著升高(P<0.01),XOD、MDA活性以及IL-1β、IL-18、TNF-α水平均显著降低(P<0.01),踝关节组织中ROS水平和TXNIP、NLRP3、ASC蛋白表达水平均显著降低(P<0.05或P<0.01)。苏萸痛风方中、低剂量组上述部分指标活性/水平也发生显著逆转(P<0.05或P<0.01)。结论苏萸痛风方可通过ROS/TXNIP/NLRP3信号通路,抑制NLRP3炎性小体激活,进而发挥抗痛风性关节炎的作用。
ABSTRACT: OBJECTIVE To study the mechanism of Suyu tongfeng prescription against gouty arthritis . METHODS Male SD rats were randomly divided into normal control group ,model group ,colchicine tablets group (positive control drug ,0.3 mg/kg) and high -dose,medium-dose and low -dose groups (5,2.5,1.25 g/kg)of Suyu tongfeng prescription according to body mass ,with 10 rats in each group . The rats in the administration group were orally given the corresponding drugs once a day (10 mL/kg)for 7 consecutive days . Rats in the normal control group and model group were given equal volume of water intragastrically . On the 6th day,1 h after administration ,except for normal control group ,the rats in other groups were injected with sodium urate into the joint to replicate the gouty arthritis model . The degree of joint swelling and the score of inflammatory indexes were measured at 2, 6 and 24 h after the establishment of the model . One hour after the last administration ,the activity of oxidative stress related indicators [superoxide dismutase (SOD),xanthine oxidase (XOD),malondialdehyde(MDA)] and the levels of inflammatory factors [interleukin 1β(IL-1β),IL-18,tumor necrosis factor α were detected in the serum . The histopathological changes of ankle joints in each group were observed ;the expressions level of thioredoxin interacting protein (TXNIP), mail:150120239@qq.com NOD like receptor thermoprotein domain related protein 3 (NLRP3),apoptosis related spot like protein (ASC)in the @qq.com ankle joint of rats were detected . RESULTS After intervened with Suyu tongfeng prescription ,the swelling degree of joints ,the score of inflammation indexes ,the edema of synovial tissue and the amount of inflammatory cells were reduced . The activity of SOD in Suyu tongfeng prescription high -dose group was increased significantly(P<0.01),while the activities of XOD and MDA as well as the levels of IL -1β,IL-18 and TNF -α were all decreased significantly(P<0.01). The level of ROS and the protein expressions of TXNIP ,NLRP3 and ASC in ankle joint were all decreased significantly (P<0.05 or P<0.01). The activities/levels of the above indexes were also significantly reversed in the middle-dose and low -dose groups of Suyu tongfeng prescription (P<0.05 or P<0.01). CONCLUSIONS Suyu tongfeng prescription can inhibit the activation of NLRP 3 inflammasome through ROS/TXNIP/NLRP 3 signaling pathway ,and then play the role of anti -gouty arthritis .
期刊: 2022年第33卷第19期
作者: 程媛,张礼,唐熠,谭亿民,李涓,宋英,袁强华,谭晓语
AUTHORS:
关键字: 苏萸痛风方;痛风性关节炎;ROS/TXNIP/NLRP3信号通路;NLRP3炎性小体;大鼠
KEYWORDS: Suyu tongfeng prescription ;gouty arthritis ;ROS/TXNIP/NLRP3 signaling pathway ;NLRP3 inflammasome;rats;
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