| 俞秋霞,姚凤,邢景,等.羟基酪醇醋酸酯对肿瘤坏死因子 α诱导类风湿关节炎成纤维样滑膜细胞增殖、迁移、侵袭及炎症反应的抑制作用[J].安徽医药,2025,29(9):1733-1738. |
| 羟基酪醇醋酸酯对肿瘤坏死因子 α诱导类风湿关节炎成纤维样滑膜细胞增殖、迁移、侵袭及炎症反应的抑制作用 |
| The inhibitory effect of hydroxytyrosol acetate on the proliferation, migration, invasion and inflammatory response of TNF-α-induced RA-FLSs |
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| DOI：10.3969/j.issn.1009-6469.2025.09.008 |
| 中文关键词: 多酚类 羟基酪醇醋酸酯 类风湿关节炎 成纤维样滑膜细胞 |
| 英文关键词: Polyphenols Hydroxytyrosol acetate Rheumatoid arthritis Fibroblast-like synoviocytes |
| 基金项目:国家自然科学基金青年科学基金项目( 82304505)；国家自然科学基金面上项目( 82371575) |
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| 中文摘要: |
| 目的探讨羟基酪醇醋酸酯( HT-AC)对肿瘤坏死因子 α(TNF-α)诱导类风湿关节炎( RA)成纤维样滑膜细胞( FLS)增殖、迁移、侵袭及炎症反应的抑制作用。方法研究时间 2023年 6―10月。不同浓度的羟基酪醇醋酸酯( 25、50和 100 μmol/L)预处理后使用 10 μg/L TNF-α诱导 RA-FLS 48 h，采用四甲基偶氮唑盐( MTT)检测细胞增殖情况，划痕实验、 Transwell细胞迁移和侵袭实验观察细胞迁移和侵袭，逆转录 -聚合酶链式反应( RT-PCR)检测神经型钙黏附蛋白( N-cadherin)、基质金属蛋白酶 3(MMP-3)和白细胞介素 -1β(IL-1β)的 mRNA表达，蛋白质印迹法检测 N-cadherin、MMP-3、IL-1β和组蛋白去乙酰化酶 3(HDAC3)的蛋白表达。结果与溶剂对照组相比， TNF-α显著促进 RA-FLS增殖［( 147.90±10.61)%比( 100.00±7.80)%］、迁移［(369.30±45.76)个比( 213.70±34.43)个］和侵袭［(143.30±17.90)个比( 71.33±16.29)个］(P<0.05)而 50或 100 μmol/L的羟基酪醇醋酸酯处理显著降低 TNF-α诱导的 RA-FLS的增殖［(129.90±7.37)%、(123.10±13.77)%］(P<0.05)，25、50或 100 μmol/L的羟基酪醇醋酸酯处理显著降低 TNF-α诱导的 RA-FLS迁移［( 273.70±37.45)个、(239.70±26.58)个、(17，8.70±19.43)个］和侵袭［( 106.00±10.00)个、(85.33±11.06)个、(72.00±7.55)个］(P<0.05)。 TNF-α显著增加 RA-FLS中 N-cadherin、MMP-3和 IL-1β的 mRNA和蛋白表达( P<0.05)而 50或 100 μmol/L的羟基酪醇醋酸酯处理显著抑制 TNF-α诱导的 RA-FLS中 N-cadherin、MMP-3和 IL-1β的 mRNA和蛋白表达(，P<0.05)。此外， 50或 100 μmol/L的羟基酪醇醋酸酯处理显著抑制 TNF-α诱导的 RA-FLS中 HDAC3的蛋白表达(P<0.05)。结论羟基酪醇醋酸酯可能通过调控 HDAC3的蛋白表达来抑制 FLS的增殖、迁移、侵袭及炎症反应在 RA疾病中发挥保护作用。 |
| 英文摘要: |
| Objective To investigate the inhibitory effect of hydroxytyrosol acetate on the proliferation, migration, invasion and in-flammatory response of fibroblast-like synoviocytes (FLSs) in patients with rheumatoid arthritis (RA) induced by TNF-α. Methods The study was conducted from June 2023 to October 2023. RA-FLSs were pretreated with different concentrations of hydroxytyrosol ac-etate (25, 50 and 100 μmol/L) and induced by 10μg/L TNF-α for 48 h. The cell proliferation was detected by methyl thiazolyl tetrazoli-um (MTT) assay, and the cell migration and invasion were observed by wound healing assay and Transwell cell migration and invasion assay. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of neural cadherin (N-cadherin), matrix metalloproteinase 3 (MMP-3) and interleukin-1β (IL-1β), and Western Blotting was used to detect the protein expres-sion levels of N-cadherin, MMP-3, IL-1β and histone deacetylase 3 (HDAC3).Results Compared with the solvent control group, TNF-α significantly promoted the proliferation [(147.90±10.61) % vs. (100.00±7.80) %], migration [(369.30±45.76) cells vs. (213.70±34.43) cells] and invasion [(143.30±17.90) cells vs. (71.33±16.29) cells] of RA-FLSs (P<0.05), while treatment with 50 or 100 μmol/L hydroxy-tyrosol acetate significantly reduced the TNF-α -induced RA-FLS proliferation [(129.90±7.37) % , (123.10±13.77) % ] (P<0.05), and treatment with 25, 50 or 100 μmol/L hydroxytyrosol acetate significantly reduced TNF-α-induced RA-FLS migration [(273.70±37.45)cells, (239.70±26.58) cells, (178.70±19.43) cells] and invasion [(106.00±10.00) cells, (85.33±11.06) cells, (72.00±7.55) cells] (P< 0.05). In addition, TNF-α significantly increased the mRNA and protein expression levels of N-cadherin, MMP-3 and IL-1β in RA-FLSs (P<0.05), while treatment with 50 or 100 μmol/L hydroxytyrosol acetate significantly inhibited the mRNA and protein expressionlevels of N-cadherin, MMP-3 and IL-1β in TNF-α-induced RA-FLSs (P<0.05). Moreover, treatment with 50 or 100 μmol/L hydroxytyro-sol acetate significantly inhibited the protein expression levle of HDAC3 in TNF-α-induced RA-FLSs (P<0.05).Conclusion Hydroxy-tyrosol acetate may play a protective role in RA diseases by regulating the protein expression of HDAC3 to inhibit the proliferation, mi-gration, invasion and inflammatory response of FLS. |
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