槲皮素调节T淋巴细胞效应对肺纤维化大鼠气道反应的作用及机制

Effect of quercetin regulating T lymphatic effect on airway response in rats with pulmonary fibrosis and its mechanism

目的:探讨槲皮素调节T淋巴细胞效应对肺纤维化大鼠气道反应的作用机制。方法:将大鼠分为对照组、模型组、槲皮素组,放射免疫测定法检测大鼠肺纤维化指标羟脯氨酸(HYP)、透明质酸(HA)、层黏连蛋白(LN)含量,ELISA检测血清中白介素17(IL-17)、白介素4(IL-4)、干扰素-γ(IFN-γ)表达,流式细胞术检测T淋巴细胞亚群变化,观察气道反应及肺组织病理学变化。结果:与对照组比较,模型组HYP、HA、LN均显著增加,肺出现组织纤维化;与模型组比较,槲皮素组大鼠HYP、HA、LN含量明显下降。模型组中IL-17、IL-4表达较对照组升高,IFN-γ表达较对照组降低;槲皮素组血清中IL-17、IL-4较模型组明显下降,IFN-γ表达较模型组明显升高。与对照组比较,模型组大鼠CD3~+、CD4~+、CD4~+/CD8~+水平明显降低,CD8~+水平升高;槲皮素组CD3~+、CD4~+、CD4~+/CD8~+水平较模型组升高,且CD8~+水平较模型组明显下降。在同等剂量mACh激发的气道反应性检测中,模型组大鼠的压力峰值-时间指数(APTI)值显著高于对照组;与模型组比较,槲皮素组APTI值明显降低。模型组肺泡结构紊乱,多数肺泡出现闭锁、裂隙、萎陷,部分融合成大肺泡,肺泡腔及间质内有炎性细胞渗出,肺泡间隔明显增宽增厚。槲皮素组较模型组肺泡腔炎症细胞浸润减轻,肺间隔略微增宽,部分肺泡融合,结构紊乱。结论:槲皮素可通过调节T淋巴细胞效应改善肺纤维化大鼠的高气道反应,进而对肺纤维化气道具有很好的治疗效果。

Objective:To explore the mechanism of quercetin regulating T lymphatic effect on airway response in rats with pulmonary fibrosis.Methods:The experimental rats were randomly divided into a control group,a model group,and a quercetin group.Radioimmunoassay was used to detect the fibrosis indexes including content of hydroxyproline(HYP),hyaluronnic acid(HA)and laminin(LN).ELISA was used to detect interleukin-17(IL-17),interleukin-4(IL-4),interferon-gamma(IFN-γ) expression.Flow cytometry was used to detect T lymphocyte subsets.Airway response,and pathological changes of lung were observed.Results:Compared with the control group,the content of HYP,HA,and LN in the model group were significantly increased,and tissue fibrosis was observed in the model group.Compared with the model group,the content of HYP,HA,and LN in the quercetin group were significantly decreased.Compared with the control group,the expression of IL-17 and IL-4 in the model group was increased,and the expression of IFN-γ was decreased.Compared with the model group,serum IL-17 and IL-4 in the quercetin group decreased,and the expression of IFN-γ was significantly increased.Compared with the control group,the levels of CD3^(+),CD4^(+) and CD4^(+)/CD8^(+) in the model group were significantly decreased,while the level of CD8^(+) was increased with statistical significance.Compared with model group,the levels of CD3^(+),CD4^(+) and CD4^(+)/CD8^(+) in the quercetin group were significantly increased,and the level of CD8^(+) was significantly decreased.In the detection of airway reactivity induced by Mach at the same dose,the APTI value of model group was significantly higher than that of control group.Compared with the model group,the APTI value of quercetin group was significantly decreased.In the model group,alveolar structure was disorganized,most alveoli were atresia,fissure,collapse,some of them fused into large alveoli,there was inflammatory cell exudation in alveolar cavity and interstitium,and alveolar septum was obviously widened and thickened.Compared with the model group,the infiltration of inflammatory cells in the alveolar cavity was reduced in the quercetin group.The pulmonary septum was slightly widened.Some alveolar fusion was disorderly.Conclusion:Quercetin can improve the hyperairway response in rats with pulmonary fibrosis by regulating the effect of T lymphocytes,and then has a good therapeutic effect on the pulmonary fibrosis airway.