CD200及其受体CD200R通路对哮喘模型大鼠气道损伤与Th1/Th2失衡的影响

doi:10.3969/j.issn.1006-6233.2025.10.09

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摘要 目的: 探究分化簇200(CD200)及其受体CD200R通路对哮喘模型大鼠的影响及其机制。方法: 将40只雄性SD大鼠随机分为对照组(给予生理盐水处理,不建模)、模型组(构建哮喘模型前给予生理盐水处理)、IgG1Fc组(构建哮喘模型前给予IgG1Fc处理)、CD200Fc组(构建哮喘模型前给予CD200Fc处理),每组10只。采用腹腔注射卵清蛋白致敏和雾化吸入激发的方法建立哮喘模型,实时荧光定量聚合酶链式反应(RT-qPCR)和蛋白质免疫印迹(Western blot)检测造模前后大鼠肺组织中CD200、CD200R的表达变化。苏木精-伊红(HE)染色观察各组大鼠肺组织病理学变化,并测量各组大鼠支气管壁厚度(Wat)和平滑肌厚度(Wam),酶联免疫吸附法(ELISA)检测各组大鼠支气管肺泡灌洗液中辅助性T细胞1(Th1)相关因子白细胞介素-12(IL-12)、干扰素-γ(IFN-γ)和辅助性T细胞2(Th2)相关因子白细胞介素-4(IL-4)、白细胞介素-13(IL-13)的水平,Western blot检测各组大鼠肺组织中T盒子转录因子(T-bet)、GATA结合蛋白3(GATA-3)的蛋白表达,流式细胞术检测各组大鼠脾脏Th1、Th2亚群分布并计算Th1/Th2比例变化。结果: 与对照组比较,模型组大鼠肺组织中CD200、CD200R的mRNA相对表达量和蛋白相对表达量均显著下调(P<0.05)。与对照组比较,模型组大鼠肺泡壁增厚、部分肺泡塌陷,气道周围有大量炎性细胞聚集,Wat和Wam显著增加(P<0.05),支气管肺泡灌洗液中IL-12和IFN-γ水平显著降低、IL-4和IL-13水平显著升高(P<0.05),肺组织中T-bet蛋白表达显著下调、GATA-3蛋白表达显著上调(P<0.05),脾脏中CD4⁺IFN-γ⁺标记的Th1和Th1/Th2显著降低、CD4⁺IL-4⁺标记的Th2显著升高(P<0.05)。与模型组比较,CD200Fc组大鼠肺泡病变、气道壁和平滑肌增厚、炎性细胞聚集等现象均明显减轻,Wat和Wam显著减小(P<0.05),支气管肺泡灌洗液中IL-12和IFN-γ水平显著升高、IL-4和IL-13水平显著降低(P<0.05),肺组织中T-bet蛋白表达显著上调且GATA-3蛋白表达显著下调(P<0.05),同时,脾脏中CD4⁺IFN-γ⁺标记的Th1和Th1/Th2显著升高、CD4⁺IL-4⁺标记的Th2显著降低(P<0.05)。 结论: 哮喘大鼠肺组织中CD200及其受体CD200R表达下调,CD200Fc预处理可以缓解哮喘大鼠气道损伤,改善Th1/Th2失衡状态,从而起到治疗作用。

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关键词 ：哮喘, CD200/CD200R通路, 气道, 炎症反应, Th1/Th2失衡

Abstract：Objective: To explore the effects of differentiation cluster 200 (CD200) and its receptor CD200R pathway on asthmatic model rats and its mechanism. Methods: A total of 40 male SD rats were randomly divided into control group (treated with normal saline without modeling), model group (treated with normal saline before building asthma model), IgG1Fc group (treated with IgG1Fc before building asthma model), and CD200Fc group (treated with CD200Fc before building asthma model), with 10 rats in each group. The asthma model was established by intrabitoneal ovalbumin sensitization and atomization inhalation stimulation. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect the expression changes of CD200 and CD200R in rat lung tissue after modeling. Hematoxylin-eosin (HE) staining was used to observe the lung histopathological changes in each group, and bronchial wall thickness (Wat) and smooth muscle thickness (Wam) were measured, Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of T helper 1 (Th1) related factors interleukin-12 (IL-12), interferon-γ (IFN-γ) and T helper 2 (Th2) related factors interleukin-4 (IL-4), interleukin-13 (IL-13) in bronchoalveolar lavage fluid of rats in each group, Western blot was used to detect the protein expression of T-box transcription factor (T-bet) and GATA binding protein 3 (GATA-3) in lung tissue of each group, Flow cytometry was used to detect the distribution of Th1 and Th2 subpopulations in spleen and to calculate the Th1/Th2 ratio. Results: Compared with the control group, the mRNA and protein relative expressions of CD200 and CD200R in lung tissues of model group were significantly down-regulated (P<0.05). Compared with the control group, the alveolar wall of the model group was thickened, part of the alveolar collapsed, and a large number of inflammatory cells gathered around the airway, Wat and Wam were significantly increased (P<0.05), the levels of IL-12 and IFN-γ in bronchoalveolar lavage fluid were significantly decreased, and the levels of IL-4 and IL-13 were significantly increased (P<0.05), the T-bet protein expression was significantly down-regulated and the GATA-3 protein expression was significantly up-regulated in lung tissue (P<0.05), CD4⁺IFN-γ⁺ labeled Th1 and Th1/Th2 were significantly decreased in spleen, and CD4⁺IL-4⁺ labeled Th2 was significantly increased (P<0.05). Compared with model group, the symptoms of alveolar lesions, thickening of airway wall and smooth muscle, and aggregation of inflammatory cells in CD200Fc group were significantly reduced, Wat and Wam were significantly decreased (P<0.05), the levels of IL-12 and IFN-γ in bronchoalveolar lavage fluid were significantly increased, the levels of IL-4 and IL-13 were significantly decreased (P<0.05), the T-bet protein expression was significantly up-regulated and the GATA-3 protein expression was significantly down-regulated in lung tissue (P<0.05), while CD4⁺IFN-γ⁺ labeled Th1 and Th1/Th2 were significantly increased and CD4⁺IL-4⁺ labeled Th2 were significantly decreased in spleen (P<0.05). Conclusion: The expression of CD200 and its receptor CD200R is down-regulated in lung tissue of asthmatic rats. Preconditioning of CD200Fc can alleviate airway injury and improve Th1/Th2 imbalance in asthmatic rats, thus playing a therapeutic role.

Key words： Asthma CD200/CD200R channel Air passage Inflammatory response Th1/Th2 imbalance

引用本文:

尼格拉·伊力哈木, 李晶晶, 努尔阿米娜·铁力瓦尔迪李新, 阿仙·乌日娜, 韩利梅. CD200及其受体CD200R通路对哮喘模型大鼠气道损伤与Th1/Th2失衡的影响[J]. 河北医学, 2025, 31(10): 1639-1645.
NIGELA Yilihamu, LI Jingjing, NUERAMINA Tieliwaerdi, et al. Effects of CD200 and Its Receptor CD200R Pathway on Airway Injury and Th1/Th2 Imbalance in Asthmatic Rats. HeBei Med, 2025, 31(10): 1639-1645.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2025.10.09 或 http://www.hbyxzzs.cn/CN/Y2025/V31/I10/1639

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