职业与健康 ›› 2023, Vol. 39 ›› Issue (21): 2907-2910.

• 论著 • 上一篇    下一篇

双氢青蒿素对脂多糖诱导的心肌成纤维细胞分泌炎性因子及NF-κB通路激活的影响

王燕1, 单铁强2, 栗志英3, 李俊娇3, 马景红3, 齐秀芳4   

  1. 1.邯郸市第二医院综合外科,河北 邯郸 056002;
    2.秦皇岛市海港医院检验科,河北 秦皇岛 066000;
    3.河北工程大学附属医院心内科,河北 邯郸 056002;
    4.邯郸市第一医院血液内科,河北 邯郸 056002
  • 收稿日期:2023-02-23 修回日期:2023-03-14 出版日期:2023-11-01 发布日期:2026-03-26
  • 通信作者: 齐秀芳,主管护师,E-mail:zxw071009@163.com
  • 作者简介:王燕,女,主管护师,主要从事综合外科护理与研究工作。

Effect of dihydroartemisinin on lipopolysaccharide induced cardiac fibroblasts inflammatory factors secretion and NF-κB pathway activation

WANG Yan1, SHAN Tieqiang2, LI Zhiying3, LI Junjiao3, MA Jinghong3, QI Xiufang4   

  1. 1. Department of Comprehensive Surgery,Handan Second Hospital,Handan Hebei 056002,China;
    2. Department of Laboratory,Qinhuangdao Haigang Hospital,Qinhuangdao Hebei 066000,China;
    3. Internal Medicine-Cardiovascular Department,Affiliate Hospital of Hebei Engineering University,Handan Hebei 056002,China;
    4. Department of Hematology,Handan First Hospital,Handan Hebei 056002,China
  • Received:2023-02-23 Revised:2023-03-14 Online:2023-11-01 Published:2026-03-26
  • Contact: QI Xiufang,Nurse in charge,E-mail:zxw071009@163.com

摘要: 目的 观察双氢青蒿素(dihydroartemisinin,DHA)对脂多糖刺激的心肌成纤维细胞(cardiac fibroblasts,CFs)增殖、分化、分泌胶原以及分泌炎性因子及核因子-κB(nuclear factor-κB,NF-κB)通路激活的影响,探究DHA抑制心脏纤维化的分子机制。方法 采用胰酶消化SD乳鼠心肌组织,获取其中的CFs。实验将CFs分为正常组(培养液)、DHA组(100 ng/mL DHA的培养液)、脂多糖组(50 μg/mL 脂多糖的培养液)、治疗组(50 μg/mL脂多糖和100 ng/mL DHA的培养液)。每组细胞同时孵育48 h后,检测各组CFs的增殖变化;ELISA定量培养液中Ⅰ型胶原(collagen type I,ColⅠ)、Ⅲ型胶原(collagen type Ⅲ,Col Ⅲ)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白介素-6(interleukin-6,IL-6)及白介素-1β(interleukin-1β,IL-1β)的水平;免疫印迹法评估胞质内平滑肌-a-肌动蛋白(a-smooth muscle actin,a-SMA)、核因子κBp65(nuclear factor κBp65,NF-κBp65)及磷酸化核因子κBp65(phosphorylated nuclear factorκBp65,p-NF-κBp65)的水平。结果 与正常组对比,DHA组的细胞增殖、培养液中ColⅠ、Col Ⅲ、TNF-α、IL-6及IL-1β的含量,胞质内a-SMA、NF-κBp65及p-NF-κBp65蛋白含量及NF-κBp65/p-NF-κBp65比值比较差异均无统计学意义(均P>0.05);脂多糖组细胞数目(0.122 9±0.001 4)增加,培养液中ColⅠ[(0.753 2±0.087 7)ng/L]、Col Ⅲ[(0.723 3±0.096 8)ng/L]、TNF-α[(46.78±3.60)pg/L]、IL-6[(30.08±3.93)pg/L]及IL-1β[(12.10±1.55)pg/L]含量均上升,胞质内a-SMA(0.438±0.026)、NF-κBp65(1.221±0.049)、p-NF-κBp65(1.209±0.048)的含量及NF-κBp65/p-NF-κBp65比值(0.967±0.046)均增加(均P<0.05);与脂多糖组对比,治疗组的细胞数目(0.115 6±0.001 2)减少,培养液中ColⅠ[(0.542 4±0.063 6)ng/L]、Col Ⅲ[(0.502 7±0.057 9)ng/L]、TNF-α[(25.32±3.05)pg/L]、IL-6[(19.12±3.00)pg/L]及IL-1β[(7.34±0.96)pg/L]含量均下降,胞质内a-SMA(0.208±0.020)、NF-κBp65(0.528±0.035)、p-NF-κBp65(0.206±0.026)的含量及NF-κBp65/p-NF-κBp65比值(0.412±0.025)均减少(均P<0.05)。结论 双氢青蒿素能拮抗脂多糖刺激的CFs增殖、分化、分泌胶原及炎性因子的活性,这与其能有效降低NF-κB通路活性密切相关。

关键词: 双氢青蒿素, 脂多糖, 心肌成纤维细胞, 炎性因子, NF-κB通路

Abstract: Objective To observe the effects of dihydroartemisinin(DHA) on the proliferation,differentiation,collagen secretion,inflammatory factors and NF-κB pathway activation of lipopolysaccharide induced cardiac fibroblasts(CFs),explore the molecular mechanism of DHA inhibiting cardiac fibrosis. Methods The myocardial tissue of SD suckling rats was digested with trypsin to obtain CFs. CFs were arranged into normal group(culture medium),DHA group(culture medium of 100 ng/mL DHA),lipopolysaccharide group(50 μg/mL lipopolysaccharide culture medium),the treatment group(50 μg/mL lipopolysaccharide and 100 ng/mL DHA).After 48 h incubation of cells in each group,the proliferation of CFS in each group was detected. The ELISA was used to quantify the level of collagen typeⅠ(ColⅠ),collagen type Ⅲ(Col Ⅲ),tumor necrosis factor α(TNF-α),interleukin-6(IL-6) and interleukin-1β(IL-1β) in the culture medium. The immunoblotting was used to evaluate intracellular smooth muscle-a-actin(a-SMA),nuclear factorκB p65(NF-κBp65),and phosphorylated nuclear factorκB p65(p-NF-κBp65). Results The cell proliferation,the content of colⅠ,col Ⅲ,TNF-α,IL-6 and IL-1β in suspension,protein content of a-SMA,NF-κBp65 and p-NF-κBp65 and NF-κBp65/p-NF-κBp65 ratio in intracytoplasmbetween DHA group and normal group had not obviously difference(all P>0.05). Compared with the normal group,the number of cells in lipopolysaccharide group(0.122 9±0.001 4) increased,and the contents of colⅠ[(0.753 2±0.087 7)ng/L],col Ⅲ[(0.723 3±0.096 8)ng/L],TNF-α[(46.78±3.60)pg/L],IL-6[(30.08±3.93)pg/L] and IL-1β[(12.10±1.55)pg/L] in suspension increased,and the intracytoplasm contents of a-SMA(0.438±0.026),NF-κBp65(1.221±0.049),p-NF-κB p65(1.209±0.048) and NF-κBp65/p-NF-κBp65 ratio(0.967±0.046) increased(all P<0.05). Compared with the lipopolysaccharide group,the number of cells(0.115 6±0.001 2) decreased in treatment group,and the levels of colⅠ[(0.542 4±0.063 6) ng/L],col Ⅲ[(0.502 7±0.057 9)ng/L],TNF-α[(25.32±3.05)pg/L],IL-6[(19.12±3.00)pg/L] and IL-1β[(7.34±0.96)pg/L] decreased in suspension,and the intracytoplasm contents of a-SMA(0.208±0.020),NF-κBp65(0.528±0.035),p-NF-κBp65(0.206±0.026) and NF-κBp65/p-NF-κBp65 ratio(0.412±0.025) decreased(all P<0.05). Conclusion The dihydroartemisinin can inhibit the proliferation,differentiation,secretion of collagen and inflammatory factors of CFS stimulated by lipopolysaccharide,which isclosely related to the effective reduction the activity of of NF-κB pathway.

Key words: Dihydroartemisinin, Lipopolysaccharide, Cardiac fibroblasts, Inflammatory factors, NF-κB pathway

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