【作者】 秦鑫；

【导师】 刘卓拉；

【作者基本信息】 山西医科大学 ， 呼吸内科， 2003， 硕士

【摘要】 目的：探讨Th1／Th2、TC1／TC2失衡在哮喘发病机制中的作用，了解IFN-γ和糖皮质激素对其的影响。方法：采用Ficoll-Hypague密度梯度离心及贴壁培养法对18例哮喘患者和10例健康对照者外周血单个核细胞进行分离，纯化后，加入地塞米松及IFH-γ培养24小时，加入PMA，莫能菌素，艾罗霉素培养4.5小时，促使细胞内细胞因子聚集于高尔基体，取培养上清中的淋巴细胞经流式细胞仪检测分析CD4+T、CD8+T淋巴细胞及其细胞内细胞因子IL-2、IL-10、TGF-β表达率。结果：(1)CD4+T细胞亚群TH1、TH2、TH3及TH1／TH2检测结果的比较。哮喘组TH1，TH2与正常对照组比较，均显著增加(P＜0.05)，TH1／TH2显著降低(P＜0.05)，TH3显著增加(P＜0.05)。加入地塞米松培养的哮喘组TH1，TH2均显著降低(P＜0.05)，TH1／TH2无显著差异(P＞0.05)，TH3无显著差异(P＞0.05)。加入IFN-γ培养的哮喘组TH1显著增加(P＜0.05)，TH2差异无显著性(P＞0.05)，TH1／TH2显著增加(P＜0.05)，TH3显著降低(P＜0.05)。(2)CD8+T细胞亚群TC1、TC2、TC1／TC2检测结果的比较。哮喘组TC1，TC2与正常对照组比较，均显著增加山西省医科大学硕士毕业论文(P(0.05)，TClffCZ显著增加(P(0.05)。加人地塞米松培养的哮喘组TCI，TCZ均显著降低(P<0 .05)，TCI汀C2无显著差异(P>0.05)。加人IFN一y培养的哮喘组TCI显著增加(P<0.05)，TCZ差异无显著性(P>0.05)，TCI厅C2显著增加(P<0.05)。(3)CDs+T叮一乒及CE吟、CDS细胞内总TGF一乒检测结果的比较。哮喘组CDS十TGF一月与正常对照组比较，显著增高(P<0.05);加人地塞米松培养的哮喘组CDS+TGF一日显著降低(P<0.05)，加人IFN培养的哮喘组CDS+TGF一尽的变化显著降低，(P<0.05)，CD4、CDS细胞内总TGF一p哮喘比正常组显著增加(P<0.05)，加地塞米松后无显著变化(P>0.05)，加IFN一y后显著降低(P<0 .05)。结论:(1)哮喘急性发作期有THI汀H2、TCI汀C2的比例失衡。(2)地塞米松可通过抑制哮喘T淋巴细胞产生细胞因子缓解哮喘的炎症反应，但并不能纠正THI汀H2、TCI/TC2的比例失衡，而且也不能降低气道重塑。(3)IFN一y可通过纠正THI/TH2、TCI汀C2的比例失衡及抑制TGF一日的分泌治疗哮喘，降低哮喘气道重塑。更多还原

【Abstract】 Objective: To investigate the imbalance of TH1/TH2,TC1/ TC2 in peripheral blood of bronchial asthma and their variation under dexamethasone or IFN-7. Methods: Peripheral blood mononuclear cells from 18 asthmatic patients and 10 normal donors were isolated by density centrifugation with Ficoll - Hypague and cultivated with or without dexamethasone,IFN - γ respectively for 24 hours. Untill the 19. 5th hours,PMA,Monesin and Ionomycin were added into the cultive palate for continuing 4.5 hours. Then,CD4+T,CD8+T and their intracellular cytokine such as IL2,IL10,TGF-β were analysed by Flow cytometery. Results: (1) The frequencies of TH1 and TH2 in asthmatic group were significantly increased than that in normal control group, TH1/TH2 lower, TH3 higher. The percentages of TH1 and TH2 in asthmatic group stimulated with dexamethasone were significantly decreased than those in asthmatic control group, but TH1 /TH2 and TH3 no significant difference. The frequencies of TH1 in asthmatic group stimulated with IFN-γ were significantly increased than that in asthmatic control group, TH2 no significant difference, TH1/TH2 significantly increased, and TH3 significantly decreased. (2) The frequencies of Tc1 and Tc2 in asthmatic group were significantly increased than those in normal control group,Tc1/Tc2 higher. The percentages of Tc1 and Tc2 in asthmaticgroup stimulated with dexamethasone were significantly decreased than those in asthmatic control group, but Tc1/Tc2 no significant difference. The frequency of Tc1 in asthmatic group stimulated with IFN-γ was significantly increased than that in asthmatic control group, Tc2 no significant difference, Tc1/Tc2 significantly increased . (3) The frequencies of CD8 + TGF-β in asthmatic group were significantly increased than that in normal control group. The percentages of CD8 + TGF -β in asthmatic group stimulated with either dexamethasone or IFN -γ were all significantly decreased than that in asthmatic control group, while in asthmatic group, TGF -β stimulated with dexmethasone in both CD4 + T and CD8 + T was not significant difference. The frequency of CD8 + TGF - β in asthmatic group stimulated with IFN -γ has no significant difference than that in asthmatic control group. Conclusion: (1)There are the imbalances of TH1/TH2 and TC1/TC2 in peripheral blood of acute asthmatic patients. (2)The production of cytokine by CD4 + T can be suppressed by dexamethasone Which can neither reverse the imbalance ofTh1/Th2 and Tc1/Tc2 nor alleviate the airway remodeling. (3) IFN -γ may play a therapic role on asthma by reversing the imbalance of Th1/Th2 and Tc1/Tc2 and reducing the production of TGF - βin Lymph-ocyte which was thought to being related to asthmatic airway remodeling.更多还原