常山酮对小鼠子宫内膜异位症巨噬细胞极化的调控作用

doi:10.6040/j.issn.1671-7554.0.2016.149

摘要/Abstract

摘要： 目的探讨常山酮(HF)对小鼠子宫内膜异位症(EMs)中巨噬细胞极化的调控作用。方法构建EMs小鼠模型,观察并计算小鼠异位灶体积。流式细胞术检测巨噬细胞标志物,包括M1型(CD16/32⁺, CD197⁺)和M2型(CD206⁺, CD14⁺);Western blotting检测巨噬细胞标志蛋白,包括M1型(iNOS, IL-12)和M2型(Arg-1, IL-10)的表达;ELISA检测各炎症因子水平,最后TGF-β1诱导单独分离的巨噬细胞,Western blotting和流式细胞术分别检测iNOS和Arg-1的表达及阳性细胞数目。结果 HF抑制EMs鼠异位内膜的体积增加;使M1型细胞数目增加,M2减少;M1型标志蛋白的表达增加,M2降低;促炎因子含量升高,抑炎因子含量降低;HF使TGF-β1诱导的巨噬细胞中iNOS⁺细胞数目增加,IL-10⁺减少。结论 HF可直接作用于巨噬细胞,维持EMs模型鼠炎症微环境的平衡,抑制巨噬细胞向M2型极化,减少EMs鼠异位内膜体积。

关键词: 子宫内膜异位症, 常山酮, 炎症因子, 巨噬细胞

Abstract: Objective To explore the effect of Halofuginone(HF)on macrophage polarization in endometriosis(EMs)mouse. Methods EMs mouse model was established. The lesion size was observed and calculated. The macrophage markers, including M1 phenotype(CD16/32⁺, CD197⁺)and M2 phenotype(CD206⁺, CD14⁺), were measured by flow cytometry. The expressions of macrophage molecules, including M1 phenotype(iNOS, IL-12)and M2 phenotype(IL-10, Arg-1), were detected by Western Blot. The levels of cytokines were measured by ELISA. Finally, the separated macrophages were treated with TGF-β1 and the expressions of iNOS and Arg-1 were examined by Western Blot. Moreover, the positive cell number was detected by flow cytometry. Results HF decreased the lesion seize in EMs mouse. The numbers of M1 phenotype were increased and M2 were reduced. The expressions of M1 markers were promoted, and the expressions of M2 were restrained with HF treatment. The levels of pro-inflammation cytokines were increased with decreased level of anti-inflammation cytokines by HF. The cell numbers of iNOS⁺ were increased and Arg-1 were decreased in TGF-β1 treated macrophages. Conclusion HF directly affects macrophages, maintains the balance of inflammatory microenvironment in EMs mouse, suppresses the macrophages polarization towards M2 phenotype, reduces the lesion seize of EMs mouse.

Key words: Halofuginone, Macrophage, Endometriosis, Inflammatory cytokine

中图分类号:

R711.71

杨延军,梁静,李芳,杜令席. 常山酮对小鼠子宫内膜异位症巨噬细胞极化的调控作用[J]. 山东大学学报（医学版）, 2016, 54(9): 26-31.

YANG Yanjun, LIANG Jing, LI Fang, DU Lingxi. Effect of halofuginone on macrophage polarization in endometriosis mouse[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(9): 26-31.

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