首页|槲皮素通过抑制HMGB1/TLR4信号通路减轻急性支气管炎大鼠炎症反应

槲皮素通过抑制HMGB1/TLR4信号通路减轻急性支气管炎大鼠炎症反应

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目的 探讨槲皮素(QUE)对急性支气管炎(AB)大鼠炎症反应及高迁移率族蛋白B1/Toll样受体4(HMGB1/TLR4)信号通路的影响。方法 构建AB大鼠模型,将造模成功大鼠随机分为AB组、槲皮素低、高剂量组(QUE-L、QUE-H组)、槲皮素高剂量+HMGB1重组蛋白组(QUE-H+r-HMGB1组),另取剩余正常健康大鼠作为对照组(Control组);瑞氏染色检测肺泡灌洗液(BALF)沉淀物中炎性细胞数目;ELISA检测BALF中炎症因子水平;流式细胞术检测BALF中CD4+T、CD8+T及CD4+T/CD8+T值;HE染色观察支气管组织及肺组织病理形态;Western blot检测HMGB1/TLR4信号通路相关蛋白表达。结果 AB组较Control组支气管管腔内分泌物增多,管腔狭窄,管壁炎细胞浸润明显,支气管黏膜上皮细胞脱落、变性,平滑肌层增厚明显,肺泡壁增厚,肺泡间隔增宽,炎性细胞浸润明显,NEU、EOS、LYM数目和TNF-α、IL-6、CD4+T、CD4+T/CD8+T水平及HMGB1、TLR4、p-NF-κB p65/NF-κB p65表达升高,IL-10、CD8+T水平降低(P<0。05);QUE-L、QUE-H组较AB组支气管管腔内分泌物减少,管壁相对完整,支气管黏膜上皮细胞脱落、变性轻微,平滑肌增厚情况、肺泡壁增厚情况、肺泡间隔增宽情况、炎症细胞浸润程度减轻,NEU、EOS、LYM数目和TNF-α、IL-6、CD4+T、CD4+T/CD8+T水平及HMGB1、TLR4、p-NF-κB p65/NF-κB p65表达降低,IL-10、CD8+T水平升高(P<0。05);QUE-H+r-HMGB1组较QUE-H组支气管和肺组织病理损伤加重,NEU、EOS、LYM数目和TNF-α、IL-6、CD4+T、CD4+T/CD8+T水平及HMGB1、TLR4、p-NF-κB p65/NF-κB p65表达升高,IL-10、CD8+T水平降低(P<0。05)。结论 槲皮素可减轻AB大鼠炎症反应,其作用机制与抑制HMGB/TLR4信号通路相关。
Quercetin alleviates inflammation in acute bronchitis rats by inhibiting HMGB1/TLR4 signaling pathway
To investigate the effects of Quercetin(QUE)on inflammatory response and high mobility group protein B1/Toll like receptor 4(HMGB1/TLR4)signaling pathway in acute bronchitis(AB)rats,an AB rat model was constructed,and the successfully modeled rats were assigned into AB group,quercetin low and high dose groups(QUE-L,QUE-H groups),Quercetin high dose+HMGB1 recombinant protein group(QUE-H+r-HMGB1 group),with remaining normal healthy rats as control group.Wright's staining was applied to detect the number of inflammatory cells in the sediment of bronchoalveolar lavage fluid(BALF);ELISA was applied to detect the levels of inflammatory factors in BALF;flow cytometry was used to detect the levels of CD4+T,CD8+T and CD4+T/CD8+T in BALF;HE staining was applied to observe the pathological morphology of bronchial tissue and lung tissue;Western blot was applied to detect the expression of proteins related to the HMGB1/TLR4 signaling pathway.Compared with the control group,the AB group had increased secretion in the bronchial lumen,narrowed lumen,obvious infiltration of inflammatory cells in the wall,shedding and degeneration of bronchial mucosal epithelial cells,obvious thickening of smooth muscle layer,thickening of alveolar wall,widening of alveolar septum,and obvious infiltration of inflammatory cells,increased numbers of NEU,EOS,LYM,and elevated levels of TNF-α,IL-6,CD4+T,CD4+T/CD8+T,and increased expression of HMGB1,TLR4,p-NF-κB p65/NF-κB p65,while lower levels of IL-10 and CD8+T(P<0.05).QUE(both low and high doses)could alleviate these changes mentioned above in AB rats(P<0.05).As compared with QUE-H group,QUE-H+r-HMGB1 group demonstrated more severe pathological damage of bronchial and lung tissues,increased numbers of NEU,EOS and LYM,higher levels of TNF-α,IL-6,CD4+T and CD4+T/CD8+T,and higher expression of HMGB1,TLR4 and p-NF-κB p65/NF-κB p65 increased,while lower levels of IL-10 and CD8+T(P<0.05).Taken together,quercetin can alleviate the inflammatory response in AB rats,and its mechanism of action is related to the inhibition of the HMGB/TLR4 signaling pathway.

QuercetinHigh mobility group protein B1/Toll-like receptor 4 signaling pathwayAcute bronchitisInflammatory response

梅豆、田辉

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430010,武汉市中医医院急诊科

430010,武汉市中医医院呼吸内科

槲皮素 高迁移率族蛋白B1/Toll样受体4信号通路 急性支气管炎 炎症反应

2024

免疫学杂志
第三军医大学,中国免疫学会

免疫学杂志

CSTPCD
影响因子:0.704
ISSN:1000-8861
年,卷(期):2024.40(6)