| 引用本文:范嘉懿，高一煊，梁蓝云，贾凯杰，刘春红，韩洁茹.资生肾气丸对尿酸钠诱导大鼠滑膜细胞中P62/Nrf2通路调控机制的研究[J].世界中医药,2025,(03):. |
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| 资生肾气丸对尿酸钠诱导大鼠滑膜细胞中P62/Nrf2通路调控机制的研究 |
| Regulatory Mechanism of Zisheng Shenqi Pills on the P62/Nrf2 Pathway in Sodium Urate-induced Synoviocytes of Rats |
| 投稿时间：2024-05-09 |
| DOI：10.3969/j.issn.1673-7202.2025.03.007 |
| 中文关键词: 资生肾气丸 痛风性关节炎 成纤维样滑膜细胞 尿酸单钠晶体 p62/核因子E2相关因子2（Nrf2）信号通路 Nod样受体家族pyrin结构域蛋白3炎症小体 3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐 实验研究 |
| English Keywords:Zisheng Shenqi Pills Gouty arthritis Fibroblast-like synoviocytes Monosodium urate crystal P62/nuclear factor erythroid 2-related factor 2(Nrf2) signaling pathway NOD-like receptor protein 3(NLRP3) inflammasome 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) Experimental research |
| 基金项目:国家自然科学基金项目（81704055）——基于自噬p62/Keap-1/Nrf2-NLRP3炎症小体途径研究资生肾气丸改善痛风性关节炎的作用机制;黑龙江中医药优秀青年骨干教师支持计划2019；黑龙江中医药优秀青年骨干教师支持计划2019（15041190026）——“以学生为中心”的多元结合温病学教学模式研究 |
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| 中文摘要: |
| 目的：探讨资生肾气丸对尿酸单钠晶体（MSU）诱导的痛风性关节炎大鼠成纤维样滑膜细胞（GA-FLS）P62/Nrf2信号转导通路的影响。方法：按随机数字表法将18只雄性SD大鼠分为中药低、中、高3种剂量组，每组6只，连续灌胃7 d后，统一麻醉，分离血清备用，用低、中、高3种剂量的含药血清体外干预GA-FLS，设为正常滑膜细胞组，MSU组，GA-FLS+中药低、中、高剂量组，共5组，用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)比色法检测细胞增殖能力；蛋白质免疫印迹法检测P62、Kelch样ECH相关蛋白-1（Keap-1）、核因子E2相关因子2（Nrf2）含量；RT-PCR检测P62、Nrf2含量。结果：MTT结果表明，与模型组比较，各剂量资生肾气丸含药血清组FLS细胞增殖均受到抑制，其中高剂量差异有统计学意义(P<0.01)；蛋白质免疫印迹法结果显示，就p62、Nrf2、NLRP3蛋白的表达水平度而言，模型组相对于空白组明显增高（均P<0.01）；与模型组比较，低、中、高资生肾气丸含药血清组蛋白表达含量均降低（均P<0.05）；RT-PCR结果显示，与空白组比较，模型组细胞中p62、Nrf2表达明显升高（均P<0.01）；与模型组比较，加入中药血清滑膜细胞中，p62、Nrf2表达下降（均P<0.05）。结论：资生肾气丸可通过调控P62/Nrf2信号转导通路抑制GA-FSL细胞增殖，下调P62、Keap-1、Nrf2蛋白的表达、抑制Nod样受体家族pyrin结构域蛋白3（NLRP3）炎症小体产生，具有抗炎作用，从而对GA具有防治效果。 |
| English Summary: |
| To investigate the effects of Zisheng Shenqi Pills on the P62/nuclear factor erythroid 2-related factor 2(Nrf2) signaling pathway in fibroblast-like synoviocytes(FLS) from rats with monosodium urate(MSU)-induced gouty arthritis(GA).Methods:Eighteen male SD rats were randomly divided into three groups receiving low，medium，and high doses of Zisheng Shenqi Pills(n=6 per group) according to a random number table.After continuous intragastric administration for seven days，rats were anesthetized together and blood serum was collected.GA-FLS were interfered in vitro with low，medium and high doses of drug-containing serum.Five experimental groups were established：normal synoviocyte group，MSU model group，and GA-FLS groups treated with low，medium，and high doses of drug-containing serum.Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay，while protein expression levels of P62，Kelch-like ECH-associated protein-1(Keap-1)，and Nrf2 were analyzed by Western blot.Additionally，P62 and Nrf2 mRNA levels were measured via RT-PCR.Results:The MTT assay showed that FLS proliferation was inhibited in all Zisheng Shenqi Pills-containing serum groups compared to the model group，with a statistically significant difference observed in the high-dose group(P<0.01).Western blot analysis indicated that the protein levels of P62，Nrf2，and NOD-like receptor protein 3(NLRP3) were significantly elevated in the model group compared to the normal group(P<0.01)，while treatment with Zisheng Shenqi Pills-containing serum significantly reduced their expression levels across all dose groups(P<0.05).RT-PCR results further confirmed that P62 and Nrf2 mRNA levels were significantly increased in the model group compared to the normal group(P<0.01)，whereas drug-containing serum treatment led to a significant decrease in their expression(P<0.05).Conclusion:Zisheng Shenqi Pills exert anti-inflammatory effects by regulating the P62/Nrf2 signaling pathway，inhibiting GA-FLS proliferation，downregulating P62，Keap-1，and Nrf2 protein expression，and suppressing NLRP3 inflammasome activation，thereby providing a protective and therapeutic effect against GA. |
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