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红景天苷对TNF-α诱导的人类风湿关节炎成纤维样滑膜细胞增殖的抑制作用及其意义 被引量:17

Inhibitory effect of salidroside on proliferation of HFLS-RA induced by TNF-αand its significance
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摘要 目的:探讨红景天苷对肿瘤坏死因子α(TNF-α)诱导的人类风湿关节炎成纤维样滑膜细胞(HFLS-RA)增殖的抑制作用,阐明其控制类风湿关节炎(RA)的分子机制。方法:体外培养HFLS-RA,采用TNF-α及不同浓度红景天苷处理细胞,分为正常对照组(0.0μg·L^(-1) TNF-α)、模型对照组(10.0μg·L^(-1)TNF-α)及12.5、25.0、50.0、100.0μmol·L^(-1)红景天苷组(10.0μg·L^(-1) TNF-α+相应浓度红景天苷)。MTT法检测HFLS-RA的增殖活力,ELISA法检测细胞上清液中β-catenin、基质金属蛋白酶7(MMP-7)和Cyclin-D1表达水平,Western blotting法检测细胞中β-catenin蛋白表达水平。结果:与正常对照组比较,模型对照组HFLS-RA增殖活力明显升高(P<0.05)。与模型对照组比较,12.5和25.0μmol·L^(-1)红景天苷组HFLSRA增殖活力虽降低,但组间比较差异无统计学意义(P>0.05);50.0和100.0μmol·L^(-1)红景天苷组HFLSRA增殖活力降低(P<0.05)。与正常对照组比较,模型对照组细胞上清液中β-catenin、MMP-7和Cyclin-D1表达水平明显升高(P<0.05)。与模型对照组比较,12.5和25.0μmol·L^(-1)红景天苷组细胞上清液中β-catenin、MMP-7和Cyclin-D1表达水平虽降低,但组间比较差异无统计学意义(P>0.05);50和100μmol·L^(-1)红景天苷组细胞上清液中β-catenin、MMP-7和Cyclin-D1表达水平明显降低(P<0.05)。Western blotting法检测,模型对照组细胞中β-catenin蛋白表达水平明显高于正常对照组(P<0.01);12.5和25.0μmol·L^(-1)红景天苷组细胞中β-catenin蛋白表达水平虽低于模型对照组,但组间比较差异无统计学意义(P>0.05);50.0和100.0μmol·L^(-1)红景天苷组细胞中β-catenin蛋白表达水平低于模型对照组(P<0.05)。结论:红景天苷可抑制HFLS-RA的增殖,其控制RA的机制可能与Wnt/β-catenin信号通路的调控有关联。 Objective: To study the inhibitory effect of salidroside on the proliferation of fibroblast-like synoviocytes with rheumatoid arthritis in human (HFLS-RA) induced by tomor necrossi factor-α (TNF-α), and to clarify the molecular mechanism of its control effect on rheumatoid arthritis (RA). Methods: The HFLS-RA were cultured in vitro, then treated with TNF-a and different concentrations of salidroside. The cells were divided into normal control group (0 μg ~ L-1TNF-a), model control group (10.0 μg ~ L-1TNF-α) and 12.5, 25.0, 50.0, and 100. 0 μmol · L-^1 salidroside groups (10.0 μg · L^-1 TNF-a + salidroside). The proliferation activity was detected by MTT mehthod; the expression levels of la-catenin, matrix metalloproteinase-7 (MMP-7), and Cyclin- D1 in supernatant of the cells were detected by ELISA methodl the expression level of β-catenin protein in cells was detected by Western blotting method. Results: Compared with normal control group, the proliferation activity of the HFLS-RA in model control group was significantly increased (P《0.05) I compared with model control group, the proliferation activities of the HFLS-RA in 12.5 and 25.0 btmol · L ^-1 salidroside groups were decreased but there were no significant differences (P 〉 0. 05), and the proliferation activities of the HFLS-RA in 50.0 and 100.0 btmol- L ^-1salidroside groups were significantly decreased (P〈 0.05). Compared with normal control group, the expression levels of 13-catenin, MMP-7, and Cyclin-D1 in the supernatant of the cells in model control group were increased (P 〈0.05). Compared with model control group, the expression levels of β-catenin, MMP-7, and Cyclin- D1 in the supernatant of the cells in 12.5 and 25.0 μmol · L-^1 salidroside groups were decreased, but there were no significant differences (P〉0.05)i the expression levels of β-catenin, MMP-7, and Cyclin- D1 in the supernatant of the cells in 50. 0 and 100.0 μmol · L^-1 salidroside groups were decreased (P〈0.05). The Western blotting results showed that the expression level of β-catenin protein in the cell in model control group was higher than that in normal control group (P〈0.01) ; the expression levels of β-eatenin protein in the cells in 12.5 and 25.0 μmol · L-1 salidroside groups were lower than that in model control group, but there were no significant differences (P〉0.05) ; the expression levels of β-catenin protein in the cells in 50.0 and 100.0 μmol. L-1 salidroside groups were lower than that in model control group (P〈0.05). Conclusion: Salidroside could inhibit the proliferation of HFLS-RA, and its control effect might be related to the regulation of Wnt/β- catenin single pathway.
作者 郑洋洋 代东雪 潘志 唐成芳 王颖航 ZHENG Yangyang DAI Dongxue PAN Zhi TANG Chengfang WANG Yinghang(Department of Chinese Internal Medicine, College of Clinical Medicine, Changchun University of Chinese Medicine, Changchun 130021, China Research and Development Center of Traditional Chinese Medicine and Bioengineering, Changchun University of Chinese Medicine, Changchun 130117, China Department of Rheumatism, Affiliated Hospital, Changchun University of Chinese Medicine, Changchun 130021, China)
出处 《吉林大学学报(医学版)》 CAS CSCD 北大核心 2017年第3期485-490,共6页 Journal of Jilin University:Medicine Edition
基金 国家自然科学基金资助课题(81273651 81374025) 吉林省中医药管理局科研项目资助课题(2014-ZC44)
关键词 类风湿关节炎 红景天苷 成纤维样滑膜细胞 肿瘤坏死因子Α WNT/Β-CATENIN信号通路 rheumatoid arthritis salidroside fibroblast-like synoviocytes tumor necrosis factor alpha Wnt/β-catenin signaling pathway
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