Effects of <italic style="font-style: italic">β</italic>-sitosterol on the function of synovial fibroblasts in rheumatoid arthritis and its mechanism

GU Huimin; MENG Qingliang; ZUO Ruiting; ZHAN Junping; MA Junfu; LIU Yawei

doi:10.6039/j.issn.1001-0408.2023.15.11

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Effects of β-sitosterol on the function of synovial fibroblasts in rheumatoid arthritis and its mechanism

更新时间：2023-08-10

- Effects of β-sitosterol on the function of synovial fibroblasts in rheumatoid arthritis and its mechanism
- ZHONGGUO YAOFANG Vol. 34, Issue 15, Pages: 1847-1852(2023)
- 作者机构：
  
  1.河南省中医院风湿病科，郑州　450002
  2.河南中医药大学骨伤学院，郑州　450002
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.15.11
  CLC： R965
- Published：15 August 2023，
  
  Received：27 December 2022，
  
  Revised：10 February 2023，
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谷慧敏,孟庆良,左瑞庭等.β-谷甾醇对类风湿性关节炎滑膜成纤维细胞功能的影响及机制 ^Δ[J].中国药房,2023,34(15):1847-1852.

GU Huimin,MENG Qingliang,ZUO Ruiting,et al.Effects of β-sitosterol on the function of synovial fibroblasts in rheumatoid arthritis and its mechanism[J].ZHONGGUO YAOFANG,2023,34(15):1847-1852.
谷慧敏,孟庆良,左瑞庭等.β-谷甾醇对类风湿性关节炎滑膜成纤维细胞功能的影响及机制 ^Δ[J].中国药房,2023,34(15):1847-1852. DOI： 10.6039/j.issn.1001-0408.2023.15.11.

GU Huimin,MENG Qingliang,ZUO Ruiting,et al.Effects of β-sitosterol on the function of synovial fibroblasts in rheumatoid arthritis and its mechanism[J].ZHONGGUO YAOFANG,2023,34(15):1847-1852. DOI： 10.6039/j.issn.1001-0408.2023.15.11.

摘要

目的

研究

-谷甾醇对类风湿性关节炎（RA）滑膜成纤维细胞MH7A功能的影响及其机制。

方法

使用网络药理学筛选

-谷甾醇的作用靶点及治疗RA的靶点，两者取交集后进行拓扑分析寻找治疗RA的最关键靶点。用不同浓度（0、5、10、20、40 μmol/L）的

-谷甾醇处理MH7A细胞并用CCK-8法检测细胞活性，筛选

-谷甾醇的最适给药浓度。采用10 ng/mL肿瘤坏死因子（TNF-α）体外诱导MH7A细胞后，加入

-谷甾醇（最适给药浓度）处理。CCK-8法和EdU法检测细胞增殖能力；划痕实验和Transwell侵袭法分别检测细胞迁移及侵袭能力；酶联免疫吸附测定（ELISA）法检测细胞上清液中白细胞介素1β（IL-1β）和IL-6的水平；qRT-PCR法和Western blot法分别检测过氧化物酶体增殖物激活受体α（PPARα）mRNA和蛋白表达水平。MH7A细胞转染PPARα小干扰RNA，并通过上述实验方法检测PPARα敲低后

-谷甾醇对MH7A细胞增殖、迁移、侵袭、炎症因子分泌及PPARα蛋白表达的影响。

结果

PPARα是

-谷甾醇治疗RA的最关键靶点，

-谷甾醇的最适给药浓度为20 μmol/L。与模型组相比，

-谷甾醇组MH7A细胞活力显著降低、细胞增殖数显著减少（

＜0.05），细胞迁移率显著降低、细胞侵袭数显著减少（

＜0.05），IL-1β水平、IL-6水平均显著降低（

＜0.05），PPARα mRNA和蛋白表达水平均显著增加（

＜0.05）。与阴性对照小干扰RNA组相比，敲低PPARα后细胞活力上升35.6%（

＜0.05），细胞增殖数、细胞迁移率和细胞侵袭数均显著增加（

＜0.05），IL-1β水平及IL-6水平均显著升高（

＜0.05）。

结论

-谷甾醇可以抑制TNF-α诱导的MH7A细胞的增殖、迁移、侵袭和炎症因子分泌，其作用机制与激活PPARα通路有关。

Abstract

OBJECTIVE

To investigate the effects of

-sitosterol on the function of rheumatoid arthritis （RA） fibroblastic synoviocytes MH7A cells and its mechanism.

METHODS

Network pharmacology was adopted to screen the targets of

-sitosterol and the targets for the treatment of RA. After the intersection of them， topological analysis was performed to find the most critical target in the treatment of RA. MH7A cells were treated with different concentrations （0， 5， 10， 20， 40 μmol/L） of

-sitosterol， and CCK-8 was used to assay cell viability for screening the optimal concentration of

-sitosterol. MH7A cells were induced by 10 ng/mL TNF-α

in vitro

and treated with

-sitosterol （the optimum concentration）. CCK-8 and EdU were used to detect the ability of cell proliferation. Scratch experiment and Transwell invasion assay were used to analyze cell migration and invasion. The levels of interleukin-1β （IL-1β） and IL-6 in cell supernatant were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expressions of peroxisome proliferator-activated receptor α （PPARα） were measured by qRT-PCR and Western blot， respectively. The siRNA targeting PPARα was transfected into MH7A cells， and the effects of

-sitosterol on cell proliferation， migration， invasion， the secretion of inflammatory factors and the expression of PPARα after PPARα knockdown were detected by the above experimental methods.

RESULTS

PPARα was the most critical target of

-sitosterol in the treatment of RA. The optimal concentration of

-sitosterol was 20 μmol/L. Compared with model group，

-sitosterol decreased the viability of MH7A cells， and the number of proliferating cells also decreased significantly （

＜0.05）； the cell migration rate and the number of cell invasion decreased significantly （

＜0.05）. The levels of IL-1β and IL-6 were also significantly decreased （

＜0.05）， and the mRNA and protein expression levels of PPARα were significantly increased （

＜0.05）. Compared with negative control small interfering RNA group， after PPARα knockdown， the cell viability increased by about 35.6% （

＜0.05）， the number of cell proliferation， the cell migration rate and the number of cell invasion increased significantly （

＜0.05）， and the levels of IL-1β and IL-6 also increased significantly （

＜0.05）.

CONCLUSIONS

-sitosterol could effectively inhibit the proliferation， migration， invasion and secretion of inflammatory factors in MH7A cells， the mechanism of which may be associated with activating PPARα pathway.

关键词

β-谷甾醇类风湿性关节炎过氧化物酶体增殖物激活受体α增殖迁移侵袭炎症因子

Keywords

rheumatoid arthritisperoxisome proliferator-activated receptor αproliferationmigrationinvasioninflammatory factor

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Experimental Center， School of Clinical Medicine， Changchun University of Chinese Medicine

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Effects of β-sitosterol on the function of synovial fibroblasts in rheumatoid arthritis and its mechanism

DOI：10.6039/j.issn.1001-0408.2023.15.11

摘要

Abstract

关键词

Keywords

references