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[1]杨 春,游洋伟,周 宇,等.白细胞介素-10调节辅助性T细胞17/调节性T细胞对小鼠输血相关急性肺损伤的作用研究[J].中华肺部疾病杂志,2025,(03):355-361.[doi:10.3877/cma.j.issn.1674-6902.2025.03.003]
　Yang Chun,You Yangwei,Zhou Yu,et al.Study on the effects of interleukin-10 in mice with transfusion-related acute lung injury by regulating the helper T cell 17/regulatory T cell[J].,2025,(03):355-361.[doi:10.3877/cma.j.issn.1674-6902.2025.03.003]
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白细胞介素-10调节辅助性T细胞17/调节性T细胞对小鼠输血相关急性肺损伤的作用研究(PDF)

《中华肺部疾病杂志》[ISSN:1006-6977/CN:61-1281/TN]

卷:
期数:
2025年03期
页码:
355-361
栏目:
论著
出版日期:
2025-06-25

文章信息/Info

Title:
Study on the effects of interleukin-10 in mice with transfusion-related acute lung injury by regulating the helper T cell 17/regulatory T cell
作者:
杨 春1; 游洋伟2; 周 宇2; 林泽超3; 刘 亮4; 袁 堃4
610200 成都,成都市双流区第一人民医院·四川大学华西空港医院输血科1
610200 成都,成都市双流区第一人民医院·四川大学华西空港医院检验科2
610097 成都,成都上锦南府医院病理科3
610000 成都,成都市第一人民医院呼吸与重症医学科4
Author(s):
Yang Chun1;  You Yangwei2;  Zhou Yu2;  Lin Zechao3;  Liu Liang4;  Yuan Kun4.
1Department of Blood Transfusion, The First People's Hospital of Shuangliu District, Sichuan University, West China Airport Hospital, Chengdu 610200, China; 2Department of Clinical Laboratory, The First People's Hospital of Shuangliu District, Sichuan University, West China Airport Hospital, Chengdu 610200, China; 3Department of Pathology, Chengdu Shangjin Nanfu Hospital, Chengdu 610097, China; 4Department of Respiratory and Critical Care Medicine, Chengdu First People's Hospital, Chengdu 610000, China
关键词:
小鼠;  白细胞介素-10;  Th17/Treg细胞平衡;  输血相关急性肺损伤
Keywords:
Mouse;  Interleukin-10;  Th17/Treg cells balance;  Transfusion related acute lung injury
分类号:
R563
DOI:
10.3877/cma.j.issn.1674-6902.2025.03.003
摘要:
目的 分析白细胞介素-10(IL-10)对辅助性T细胞17(Th17)/调节性T细胞(Treg)细胞平衡的影响及对小鼠输血相关急性肺损伤(TRALI)的作用。方法 将60只小鼠分为对照组、TRALI组、IL-10-L组、IL-10-H组,每组15只; 监测动脉氧分压(PaO2)、动脉血二氧化碳分庒(PaCO2),计算氧合指数(OI)及肺组织湿/干重比(W/D); 采用酶联免疫吸附法检测支气管肺泡灌洗液(BALF)炎症因子白细胞介素-6(IL-6)、干扰素-γ(INF-γ)、肿瘤坏死因子-α(TNF-α)、白细胞介素-17A(IL-17A)水平,检测BALF细胞总数及中性粒细胞比例; 检测髓过氧化物酶(MPO)活性; 采用流式细胞术检测外周血Th17/Treg细胞数量; 采用逆转录-定量聚合酶链反应(RT-qPCR)、蛋白质免疫印迹(WB)检测肺组织Th17/Treg细胞相关标志物IL-17A、维甲酸相关孤儿受体γt(RORγt)、叉头盒蛋白P3(Foxp3)、糖皮质激素诱导的肿瘤坏死因子受体相关蛋白(GITR)、细胞毒性T淋巴细胞相关蛋白4(CTLA-4)mRNA和蛋白水平。结果 与对照组相比,TRALI组PaO2、OI水平降低(t=5.921、8.216,P<0.001),PaCO2水平、肺组织(W/D)、MPO活性升高(t=10.257、7.843、3.987,P<0.001); 除对照组,每组肺组织不同程度损伤,肺泡间隔及肺泡腔内红细胞和炎性细胞不同程度增厚和浸润; 外周血Th17细胞、Th17/Treg比值上升(t=9.836、7.125,P<0.05),Treg细胞下降(t=6.254,P<0.05); 肺组织IL-17A、RORγt mRNA和蛋白水平上升(t=4.850、8.966、6.401、3.248,P<0.05),Foxp3、GITR、CTLA-4 mRNA和蛋白水平下降(t=3.567、10.190、7.632、4.610、8.789、2.436,P<0.05); BALF IL-6、INF-γ、TNF-α、IL-17A、细胞总数和中性粒细胞百分比水平升高(t=7.802、2.331、6.208、7.127、3.709、7.540,P<0.05)。与TRALI组相比,IL-10-L组和IL-10-H组PaO2、OI水平升高(P<0.001),PaCO2水平、肺组织(W/D)、MPO活性降低(P<0.001); 肺组织可见结构轻微破坏,伴有较少出血和炎症反应; 外周血Th17细胞、Th17/Treg比值下降,Treg细胞上升(P<0.05); 肺组织IL-17A、RORγt mRNA和蛋白水平下降,Foxp3、GITR、CTLA-4 mRNA和蛋白水平上升(P<0.05); BALF IL-6、INF-γ、TNF-α、IL-17A、细胞总数和中性粒细胞百分比水平下降(P<0.05)。结论 IL-10可以调节Th17/Treg细胞平衡,缓解小鼠TRALI具有意义。
Abstract:
Objective To analyze the effect of interleukin-10(IL-10)on the balance of T helper cell 17(Th17)/regulatory T cell(Treg)and its effect on mice with transfusion-related acute lung injury(TRALI). Methods Sixty mice were divided into a control group, a transfusion-related acute lung injury(TRALI)group, an interleukin-10 low-dose(IL-10-L)group, and an interleukin-10 high-dose(IL-10-H)group, with 15 mice in each group. Calculate the arterial partial pressure of oxygen(PaO2), the partial pressure of carbon dioxide(PaCO2), the oxygenation index(OI), and the wet/dry weight ratio(W/D)of lung tissues. Use the enzyme-linked immunosorbent assay(ELISA)to detect the levels of inflammatory factors in bronchoalveolar lavage fluid(BALF), including interleukin-6(IL-6), interferon-γ(INF-γ), tumor necrosis factor-α(TNF-α), and interleukin-17A(IL-17A). Detect the total number of cells and the proportion of neutrophils in BALF. Measure the activity of myeloperoxidase(MPO). Use flow cytometry to detect the number of helper T cell 17(Th17)and regulatory T cell(Treg)cells in peripheral blood. Use reverse transcription-quantitative polymerase chain reaction(RT-qPCR)and Western blotting(WB)to detect the mRNA and protein levels of Th17/Treg cell-related markers in lung tissues, including IL-17A, retinoic acid-related orphan receptor γt(RORγt), forkhead box protein P3(Foxp3), glucocorticoid-induced tumor necrosis factor receptor-related protein(GITR), and cytotoxic T lymphocyte-associated protein 4(CTLA-4). Results Compared with the control group, the levels of PaO2 and OI in the TRALI group decreased(t=5.921, 8.216, P<0.001), and the levels of PaCO2, the(W/D)of lung tissues, and the activity of MPO increased(t=10.257, 7.843, 3.987, P<0.001). Except for the control group, the lung tissues of the other groups were damaged to varying degrees. Red blood cells and inflammatory cells in the alveolar septa and alveolar cavities showed varying degrees of thickening and infiltration. The proportion of Th17 cells in peripheral blood and the Th17/Treg ratio increased(t=9.836, 7.125, P<0.05), and the proportion of Treg cells decreased(t=6.254, P<0.05). The mRNA and protein levels of IL-17A and RORγt in lung tissues increased(t=4.850, 8.966, 6.401, 3.248, P<0.05), while the mRNA and protein levels of Foxp3, GITR, and CTLA-4 decreased(t=3.567, 10.190, 7.632, 4.610, 8.789, t=2.436, P<0.05). The levels of IL-6, INF-γ, TNF-α, IL-17A, the total number of cells, and the percentage of neutrophils in BALF increased(t=7.802, 2.331, 6.208, 7.127, 3.709, 7.540, P<0.05). Compared with the TRALI group, the levels of PaO2 and OI in the IL-10-L group and the IL-10-H group increased(P<0.001), and the levels of PaCO2, the(W/D)of lung tissues, and the activity of MPO decreased(P<0.001). Slight structural damage could be seen in the lung tissues, accompanied by less bleeding and inflammatory reactions. The proportion of Th17 cells in peripheral blood and the Th17/Treg ratio decreased, and the proportion of Treg cells increased(P<0.05). The mRNA and protein levels of IL-17A and RORγt in lung tissues decreased, while the mRNA and protein levels of Foxp3, GITR, and CTLA-4 increased(P<0.05). The levels of IL-6, INF-γ, TNF-α, IL-17A, the total number of cells, and the percentage of neutrophils in BALF decreased(P<0.05). Conclusion IL-10 modulates the Th17/Treg cell balance, thereby mitigating TRALI in murine models, highlighting its potential as a therapeutic strategy.

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备注/Memo

备注/Memo:
基金项目: 四川省抗癌协会科研资金专项(齐鲁)科研课题(XH2023130)
通信作者: 袁 堃, Email: 479323959@qq.com
更新日期/Last Update: 2025-06-25