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中华肺部疾病杂志(电子版) ›› 2022, Vol. 15 ›› Issue (03) : 331 -334. doi: 10.3877/cma.j.issn.1674-6902.2022.03.009

论著

艾拉莫德通过抑制TNF-α减轻博来霉素诱导的小鼠间质性肺病
蔡欣诺1, 邵思琪1, 马华1, 周冬梅1, 潘彬1, 殷松楼1,()   
  1. 1. 221002 江苏,徐州医科大学附属医院风湿免疫科
  • 收稿日期:2021-11-23 出版日期:2022-06-25
  • 通信作者: 殷松楼
  • 基金资助:
    徐州市科技计划项目(KC16SH11)

Iguratimod decreases bleomycin-induced pulmonary fibrosis in association with inhibition of TNF-α in mice

Xinnuo Cai1, Siqi Shao1, Hua Ma1, Dongmei Zhou1, Bin Pan1, Songlou Yin1,()   

  1. 1. Department of Rheumatology and Immunology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China
  • Received:2021-11-23 Published:2022-06-25
  • Corresponding author: Songlou Yin
引用本文:

蔡欣诺, 邵思琪, 马华, 周冬梅, 潘彬, 殷松楼. 艾拉莫德通过抑制TNF-α减轻博来霉素诱导的小鼠间质性肺病[J]. 中华肺部疾病杂志(电子版), 2022, 15(03): 331-334.

Xinnuo Cai, Siqi Shao, Hua Ma, Dongmei Zhou, Bin Pan, Songlou Yin. Iguratimod decreases bleomycin-induced pulmonary fibrosis in association with inhibition of TNF-α in mice[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2022, 15(03): 331-334.

目的

观察艾拉莫德(IGU)对博来霉素(BLM)诱导的小鼠间质性肺病(ILD),分析艾拉莫德治疗ILD有效性和作用机制。

方法

C57/BL6小鼠随机分为5组:空白对照组(Normal组)、间质性肺病组(BLM组)、艾拉莫德治疗组(BLM+IGU组)、TNF-α组(BLM+TNF-α组)、TNF-α+艾拉莫德治疗组(BLM+TNF-α+IGU组);建模后BLM+IGU组和BLM+TNF-α+IGU组予90 mg/kg IGU灌胃,BLM+TNF-α组和BLM+TNF-α+IGU组腹腔注射重组鼠肿瘤坏死因子-α(rmTNF-α),每只200 ng;于第28天处死小鼠;观察小鼠体重变化;Masson染色观察肺组织病理改变;Western blot法检测相关标志物蛋白表达水平。

结果

BLM+TNF-α组小鼠体重较BLM组降低(P<0.05),BLM+TNF-α+IGU组小鼠体重较BLM+TNF-α组上升(P<0.05);Masson染色发现BLM+TNF-α组肺部胶原沉积较BLM组增多,纤维化评分升高,胶原面积增加(P均<0.05);BLM+TNF-α+IGU组胶原沉积较BLM+TNF-α组明显减少(P<0.05);BLM+TNF-α组α-SMA、MMP-2、Vimentin蛋白表达水平较BLM组升高,E-cadherin蛋白表达水平降低(P<0.05);BLM+TNF-α+IGU组较BLM+TNF-α组α-SMA、MMP-2、Vimentin蛋白表达水平降低,E-cadherin蛋白表达水平升高(P<0.05)。

结论

艾拉莫德可能通过抑制TNF-α和上皮间充质转化,减轻博来霉素引起的间质性肺病。

Objective

To investigate the impact of iguratimod (IGU) on bleomycin-induced interstitial lung disease and the related tumor necrosis factor-α (TNF-α) signaling pathway in mice to explored the effectiveness and possible mechanism of IGU in treating ILD.

Methods

Construction ILD model. C57/BL6 mice were randomly divided into 5 groups: Normal group, BLM group, BLM+ IGU group, BLM+ TNF-α group, BLM+ TNF-α+ IGU group. After the model was established, mice reveived 0.5% CMC-Na or IGU (90 mg/kg, gavage). Some BLM-treated mice were injected intra-peritoneally with PBS or recombinant murine TNF-α (200 ng per mouse) twice a week. The mice were sacrificed at day 28. Observe the change of body weight. Observe the pathological changes of lung tissue by Masson staining. Western blot was used to detect protein levels of related markers.

Results

Compared with the BLM group, the weight of the mice in BLM+ TNF-α group decreased (P<0.05), and the weight of mice in IGU treatment group higher than in BLM+ TNF-α group (P<0.05). Compared with the BLM group, Masson staining indicated increased collagen deposition increased in BLM+ TNF-α group (P<0.05), while collagen deposition in BLM+ TNF-α+ IGU group decreased compared with BLM+ TNF-α group (P<0.05). Compared with the BLM group, the protein levels of α-SMA, MMP-2, and Vimentin in the BLM+ TNF-α group increased, but E-cadherin protein level decreased (P<0.05), which were reversed by concurrent use of IGU (P<0.05).

Conclusion

IGU can regulate inflammation by inhibiting of TNF-α and EMT, and relieve interstitial lung disease caused by bleomycin.

图1 A:腹腔注射TNF-α后各组小鼠Masson染色;B:腹腔注射TNF-α后各组小鼠Ashcroft评分及胶原面积(*表示P<0.05)
图2 腹腔注射TNF-α后各组小鼠肺组织细胞外基质蛋白及EMT标记物蛋白表达水平(*表示P<0.05)
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