首页|黄连素介导NF-κB/LCN2信号通路改善COPD诱导的Th17/Treg细胞失衡

黄连素介导NF-κB/LCN2信号通路改善COPD诱导的Th17/Treg细胞失衡

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目的 通过构建慢性阻塞性肺病(COPD)大鼠模型,探讨黄连素是否通过调节NF-κB/LCN2信号通路改善COPD诱导的Th17/Treg细胞失衡.方法 将50只Wistar大鼠随机分为对照组(Control组)、慢性阻塞性肺病组(COPD组)、黄连素组(Berberine组)、黄连素+过表达对照组(Berberine+ov-NC组)和黄连素+过表达LCN2组(Berberine+ov-LCN2组),每组10只.Western blotting检测肺组织p-NF-κB、LCN2、IL-17和IL-10蛋白表达;HE染色观察大鼠肺组织病理形态变化;流式细胞术检测大鼠外周血Th17/Treg细胞比例;ELISA检测大鼠血清中IL-17和IL-10水平.结果 对照组大鼠肺组织结构完整;与Control组相比,COPD组大鼠肺组织结构损伤,肺组织中p-NF-κB和LCN2蛋白表达显著升高,外周血中Th17细胞比例显著升高,Treg细胞比例显著降低,血清中IL-17水平和肺组织中IL-17蛋白表达显著升高,血清中IL-10水平和肺组织中IL-10蛋白表达显著降低(P<0.05);与COPD组相比,Berberine组和Berberine+ov-NC组大鼠肺组织损伤改善,肺组织中p-NF-κB和LCN2蛋白表达显著降低,外周血中Th17细胞比例显著降低,Treg细胞比例显著升高,血清中IL-17水平和肺组织中IL-17蛋白表达显著降低,血清中IL-10水平和肺组织中IL-10蛋白表达显著升高(P<0.05);与Berberine组和Berberine+ov-NC组相比,Berberine+ov-LCN2组大鼠肺组织损伤加重,肺组织中LCN2蛋白表达显著升高,外周血中Th17细胞比例显著升高,Treg细胞比例显著降低,血清中IL-17水平和肺组织中IL-17蛋白表达显著升高,血清中IL-10水平和肺组织中IL-10蛋白表达显著降低(P<0.05).结论 黄连素治疗通过下调LCN2表达改善COPD大鼠肺损伤以及Th17/Treg细胞失衡,其机制可能与抑制NF-κB/LCN2信号通路有关.
Berberine mediates NF-κB/LCN2 signaling pathway to improve Th17/Treg cell imbalance induced by COPD
Objective To establish a rat model of chronic obstructive pulmonary disease(COPD),to explore whether berberine can improve the imbalance of Th17/Treg cells induced by COPD by regulating NF-κB/LCN2 signaling pathway.Methods Fifty Wistar rats were randomly divided into Control group(control group),chronic obstructive pulmonary disease group(COPD group),Berberine group(Berberine group),berberine+overexpression control group(Berberine+ov-NC group)and berberine+overexpression LCN2 group(Berberine+ov-LCN2 group),with 10 rats in each group.Western blotting was used to detect the expression of p-NF-κB,LCN2,IL-17 and IL-10 in lung tissue.HE staining was used to observe the pathological changes of lung tissue in rats.The ratio of Th17/Treg cells in peripheral blood of rats was detected by flow cytometry.The levels of IL-17 and IL-10 in serum of rats were detected by ELISA.Results In the control group,the lung tissue structure was intact;compared with the control group,the lung tissue structure of rats in COPD group was damaged,the expressions of p-NF-κB and LCN2 protein in lung tissue were significantly increased,the proportion of Th17 cells in peripheral blood was significantly increased,the proportion of Treg cells was significantly decreased,the level of IL-17 in serum and the expression of IL-17 protein in lung tissue were significantly increased,and the level of IL-10 in serum and the expression of IL-10 protein in lung tissue were significantly decreased(P<0.05).Compared with COPD group,Berberine group and Berberine+ov-NC group improved lung tissue injury,significantly decreased the expression of p-NF-κB and LCN2 proteins in lung tissue,significantly decreased the proportion of Th17 cells in peripheral blood,significantly increased the proportion of Treg cells,significantly decreased the level of IL-17 in serum and the expression of IL-17 protein in lung tissue(P<0.05).Compared with Berberine group and Berberine+ov-NC group,Berberine+ov-LCN2 group has more lung injury,higher expression of LCN2 protein in lung tissue,higher proportion of Th17 cells in peripheral blood,lower proportion of Treg cells,higher levels of IL-17 in serum and IL-17 protein expression in lung tissue,and higher levels of IL-10 in serum and IL-10 protein in lung tissue(P<0.05).Conclusion Berberine treatment can improve lung injury and Th17/Treg cell imbalance in COPD rats by down-regulating the expression of LCN2,and its mechanism may be related to the inhibition of NF-κB/LCN2 signaling pathway.

COPDBerberineTh17/Treg cell imbalanceNF-κB/LCN2 signal pathway

杨芳英、黄健、刘艳丰

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410000,湖南省长沙市第四医院呼吸与危重症医学科

慢性阻塞性肺病 黄连素 Th17/Treg细胞失衡 NF-κB/LCN2信号通路

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(7)