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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； |
| 阅读数： | 205 次 |
| 本月下载数： | 3 次 |
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