三叶青调节Th17/Treg平衡抗类风湿性关节炎的作用及机制研究

doi:10.12092/j.issn.1009-2501.2023.02.003

中国临床药理学与治疗学 ›› 2023, Vol. 28 ›› Issue (2): 138-146.doi: 10.12092/j.issn.1009-2501.2023.02.003

三叶青调节Th17/Treg平衡抗类风湿性关节炎的作用及机制研究

王铁烽1，苏洁2，王伟东3，夏荣双2，李思凡2，朱文瑞1，楼招欢2

1绍兴市中医院中药房，绍兴 312000，浙江；2浙江中医药大学药学院，杭州 311402，浙江；3浙江中医药大学附属第二医院，杭州 310005，浙江

收稿日期:2022-10-28 修回日期:2022-12-07 出版日期:2023-02-26 发布日期:2023-03-10
通讯作者: 楼招欢，女，医学博士，副研究员，研究方向：中药药理及新产品开发研究。 E-mail：zhaohuanlou@zcmu.edu.cn
作者简介:王铁烽，男，本科，主任中药师，研究方向：中药药理及中药制剂。 E-mail：wtfwtf@163.com
基金资助:
国家自然科学基金面上项目（82074457）；浙江省中医药科学研究基金项目（2020ZB266）；全国中药特色技术传承人才培训项目（T20194828003）

Mechanisms of Radix Tetrastigma on anti rheumatoid arthritis via regulating the balance of Th17/Treg

WANG Tiefeng1, SU Jie2, WANG Weidong3, XIA Rongshuang2, LI Sifan2, ZHU Wenrui1, LOU Zhaohuan2

1Pharmacy of Traditional Chinese medicine, Shaoxing Hospital of Traditional Chinese Medicine, Shaoxing 312000, Zhejiang, China; 2School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 311402, Zhejiang, China; 3The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang, China

Received:2022-10-28 Revised:2022-12-07 Online:2023-02-26 Published:2023-03-10

摘要/Abstract

摘要： 目的：探讨三叶青治疗类风湿性关节炎的可能机制。方法：采用大鼠右后足跖皮内注射弗氏完全佐剂制备类风湿性关节炎模型大鼠，灌胃给予不同剂量三叶青提取物连续3周。检测大鼠关节肿胀度、关节炎指数、关节热度、抓力；ELISA检测血浆中白介素（IL）-6、IL-17、IL-10、肿瘤坏死因子α（TNF-α）及类风湿因子（RF）水平；全自动血液流变仪检测血液流变学指标；流式细胞术测定全血中辅助性T细胞17（Th17）与调节性T细胞（Treg）比例；HE染色观察踝关节组织形态学；Western blot法检测关节滑膜组织中IL-6、RORγt、Foxp3、STAT3及p-STAT3蛋白表达。结果：三叶青能有效降低类风湿性关节炎模型大鼠关节肿胀度、关节炎指数及关节热度，升高抓力；降低Th17/Treg比例及血浆IL-6、IL-17、TNF-α、RF水平，升高IL-10水平；下调关节滑膜组织中IL-6、STAT3、p-STAT3、RORγt蛋白表达，上调Foxp3蛋白表达，改善踝关节组织形态学改变。结论：三叶青具有明显的抗类风湿性关节炎作用，其机制可能与调控IL-6/STAT3/IL-17轴调节Th17/Treg平衡有关。

关键词: 三叶青, IL-6/STAT3/IL-17轴, Th17/Treg平衡, 类风湿性关节炎

Abstract: AIM: To explore the possible mechanism of Radix Tetrastigma (RT) on anti-rheumatoid arthritis (RA). METHODS: The rat model of RA was established by intradermal injection of complete Freund's adjuvant into the right hind foot of SD rats. RT Extract with different dosage was continuous intragastric administration for 3 weeks, then, the degree of foot swelling, arthritis index score, joint heat and grip of each rat was measured respectively. ELISA was used to detect the expression levels of Interleukin (IL) 6, IL-17, IL-10, tumor necrosis factor-α, and rheumatoid factor. Fully automatic hemorheometer was applied to measure hemorheology indexes. The number of CD4+IL-17+T cells and CD4+CD25+Foxp3+T cells in peripheral blood were measured by flow cytometry. HE staining was used to observe the pathological changes of ankle joints. Western blot was used to measure expressions of IL-6, RORγt, Foxp3, STAT3 and p-STAT3 proteins in synovial tissues of joints. RESULTS: RT could significantly decrease swelling degree, arthritis index scores and joint heat of rats with RA. Grasping power of rats was improved and the serum levels of IL-6, IL-17, TNF-α and RF were significantly decreased, levels of IL-10 was increased significantly. Th17/Treg ratio in whole blood was decreased. Protein expressions of IL-6, STAT3, p-STAT3, and RORγt were down-regulated and Foxp3 protein was up-regulated in synovial tissues of joints. Functional morphology of the ankle joint of the plantar of rats with RA were significantly improved. CONCLUSION: RT has obvious anti-rheumatoid arthritis effect, and its mechanism may be related to regulating Th17/Treg balance by regulating IL-6/STAT3 axis.

Key words: radix tetrastigma, IL-6/STAT3 axis, Th17/Treg balance, rheumatoid arthritis

中图分类号:

R593.22

王铁烽, 苏洁, 王伟东, 夏荣双, 李思凡, 朱文瑞, 楼招欢. 三叶青调节Th17/Treg平衡抗类风湿性关节炎的作用及机制研究[J]. 中国临床药理学与治疗学, 2023, 28(2): 138-146.

WANG Tiefeng, SU Jie, WANG Weidong, XIA Rongshuang, LI Sifan, ZHU Wenrui, LOU Zhaohuan. Mechanisms of Radix Tetrastigma on anti rheumatoid arthritis via regulating the balance of Th17/Treg[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(2): 138-146.

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三叶青调节Th17/Treg平衡抗类风湿性关节炎的作用及机制研究

Mechanisms of Radix Tetrastigma on anti rheumatoid arthritis via regulating the balance of Th17/Treg

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