低压低氧肺动脉高压形成中CD4^(+)T细胞亚群的变化  

Changes in CD4^(+)T Lymphocyte Subsets During the Formation of Hypobaric Hypoxic Pulmonary Artery Hypertension

作　　者：秦崇 潘磊 李佳 邓会 张婧媛 QIN Chong;PAN Lei;LI Jia;DENG Hui;ZHANG Jingyuan(Department of Surgical Intensive Care Medicine,Beijing Shijitan Hospital,Capital Medical University,Beijing 100038,China;Department of Respiratory and Critical Care Medicine,Beijing Shijitan Hospital,Capital Medical University,Beijing 100038,China)

机构地区：[1]首都医科大学附属北京世纪坛医院外科重症医学科,北京100038 [2]首都医科大学附属北京世纪坛医院呼吸与危重症医学科,北京100038

出　　处：《标记免疫分析与临床》2024年第9期1580-1588,共9页Labeled Immunoassays and Clinical Medicine

基　　金：国家重大疾病多学科合作诊疗能力建设项目-老年住院患者危重症的综合治疗及管理(编号:2019YLFW)。

摘　　要：目的低压低氧性肺动脉高压患者循环中的淋巴细胞亚群发生了明显改变,探索在肺动脉高压(pulmonary hypertention,PH)形成过程的各个阶段中淋巴细胞亚群的变化。方法通过低压低氧动物实验舱模拟大鼠低压低氧性肺动脉高压的形成,分别于入舱后的3、7、14、21、28d各个节点,利用右心导管测量血流动力学、病理染色观察肺血管组织形态学、以及RT-qPCR技术检测肺组织和外周循环中CD4^(+)T淋巴细胞亚群(Th1、Th2、Th17、Treg)的改变。结果与常压常氧对照组相比,外周循环中Th1、Th2、Th17水平基本与低压低氧持续的时间成正比,而Treg在0~7d呈上升趋势,14d时较前下降,但表达仍高于常压常氧对照组,21、28d持续下降且均少于对照组;而在肺组织中,各节点Th1较对照组均明显升高、但组间差异无统计学意义,Th2在0~14d持续升高、随后下降,Th17于0~21d持续升高、随后下降,Treg在0~7d持续下降,14d时升高至对照组水平,21、28d均较前进一步升高。这与观察到的肺小血管壁增厚在0~21d内进行性加重,而21d后无明显差异性改变的趋势具有良好的相关性,此外,还在肺组织中观察到了具有代表长期免疫炎症刺激的三级淋巴结构(TLOs)也在0~21d时逐步形成、加重、维持,而28d较前趋于稳定。结论免疫炎症机制,特别是淋巴细胞亚群的失衡,可能参与了低压低氧性肺动脉高压形成过程中肺血管重塑的启动和进展,在初次进入高原环境后,积极予以抑制炎症治疗或许可以成为一种新的预防低压低氧性肺动脉高压的措施。Objective To investigate changes in lymphocyte subsets in the circulation of patients with hypobaric hypoxic pulmonary artery hypertension(HAPH)and to further clarify changes in lymphocyte subsets at various stages of pulmonary hypertension(PH)formation.Methods An animal model of HAPH was created using a hypobaric hypoxic chamber for rats.Measurements were taken at 3,7,14,21,and 28 days after exposure.Hemodynamic parameters were measured using right heart catheterization,and pulmonary vascular tissue morphology was observed through pathological staining,while changes in CD4^(+)T lymphocyte subsets(Th1,Th2,Th17,Treg)in lung tissue and peripheral circulation were detected using qRT-PCR.Results Compared with the normobaric normoxia control group,levels of Th1,Th2,and Th17 in peripheral circulation were generally proportional to the duration of hypobaric hypoxia,while Treg levels increased from 0 to 7 days,then decreased at 14 days but remained higher than in the normobaric normoxia control group,and further continued to decline at 21 and 28 days to levels lower than the control group.In lung tissue,Th1 levels were significantly higher than in the control group at all time points,without significant differences between groups.Th2 levels increased from 0 to 14 days and then decreased.Th17 levels increased from 0 to 21 days and then decreased.Treg levels decreased from 0 to 7 days,then increased to control levels at 14 days,and further increased at 21 and 28 days.These changes correlated well with the observed progressive thickening of the small pulmonary vessel walls from 0 to 21 days,which showed no significant changes after 21 days.Additionally,tertiary lymphoid organs(TLOs),indicative of chronic immune inflammation,were observed to form,worsen,and stabilize from 0 to 21 days,and tended to stabilize at 28 days.Conclusion Immune-inflammatory mechanisms,particularly the imbalance of lymphocyte subsets,could be involved in the initiation and progression of pulmonary vascular remodeling during HAPH formation.An early an

关 键 词：低压低氧性肺动脉高压 血管重塑 免疫炎症 T淋巴细胞亚群 三级淋巴结构 

分 类 号：R543.2[医药卫生—心血管疾病]