内毒素肺损伤大鼠Th1、Th2细胞凋亡的变化及其作用探讨  

Apoptosis of Th1, Th2 cells and its effects in lipopolysaccharide-induced acute lung injury in rats

作　　者：冯英凯[1] 徐剑铖[1] 杨庆华[2] 詹双齐 钱桂生[1] 

机构地区：[1]第三军医大学新桥医院全军呼吸病研究所,重庆400037 [2]重庆市卫生信息中心,400014 [3]广州军区疗养院干三科,510515

出　　处：《重庆医学》2005年第1期74-77,共4页Chongqing medicine

基　　金：国家自然科学基金资助项目 (30 0 4 0 0 2 4 )

摘　　要：目的　观察外周血与支气管肺泡灌洗液 (BALF)中Th1、Th2细胞的凋亡变化 ,并观察地塞米松 (DEX)对Th1、Th2凋亡的影响 ,从Th1、Th2凋亡的角度探讨内毒素肺损伤时机体抗炎、致炎反应的分子机制。方法　静脉注射脂多糖制作大鼠内毒素肺损伤模型。分离、提纯外周血与BALF中T淋巴细胞 ,抗大鼠CD4 :FITC标记、流式细胞仪分选后 ,应用免疫组织化学技术及TUNEL法双染动态观察外周血与BALF中Th1、Th2细胞凋亡的变化。结果　LPS致伤后 ,外周血与BALF中IFN γ阳性细胞 (Th1细胞 )与IL 4阳性细胞 (Th2细胞 )数目均减少 ,与各自凋亡细胞的比例呈显著的负相关关系 (P <0 .0 1)。DEX组IFN γ阳性细胞、IL 4阳性细胞数目均减少 ,IFN γ阳性细胞中凋亡细胞的百分数明显增加 ,与对照组比较差异非常显著 (P <0 .0 1)。IL 4阳性细胞中凋亡细胞的百分数亦增加 ,但幅度 <IFN γ阳性细胞。LPS致伤后 ,大鼠肺组织水肿及炎性病变程度进行性加重 ,与Th1向Th2漂移程度之间有关 ,但不完全平行。结论　内毒素肺损伤时 ,Th1、Th2细胞减少与凋亡有关 ;Th2细胞凋亡程度 <Th1细胞 ,可能是导致Th1/Th2漂移的原因之一。地塞米松通过调节炎症反应 ,使Th1/Th2比例趋于正常 ;Th1、Th2细胞凋亡及Th1/Th2漂移可能仅部分参与内毒素肺损伤的发生。Objective To observe apoptosis of Th1, Th2 cells in peripheral blood and in BALF in lipopolysaccharide-induced acute lung injury rat models, as well as the effects of DEX on Th1,Th2 apoptosis, and therefore to improve the understanding of the molecular mechanism for anti-inflammatory response and inflammatory response at the point of Th1/Th2 drift.Methods Acute lung injury rat models were made by applying LPS venous injection. T lymphocytes in peripheral blood and in BALF were separated and purified. After labelled with anti-rat CD4:FITC monoclone antibody and selected by flow cytometry, CD4 +T lymphocytes were detected by combination of immunohistochemistry analyses and TUNEL.Results The numbers of IFN-γ positive cells(Th1) and IL-4 positive cells(Th2) in peripheral blood and in BALF decreased after LPS challenge. There was a negative corelative relationship between the percentage of Th1,Th2 cells and their respective apoptotic cells among them(P<0.01). The numbers of IFN-γ positive cells and IL-4 positive cells decreased in dexamethasone(DEX) group. The percentage of apoptotic cells among IL-4 positive cells increase significantly, and there was a remarkable difference between the DEX group and the saline control group. By comparison, the raising level of the percentage of IL-4 positive cell apoptosis was lower. The edema severity and pathological changes of pulmonary tissues were excessively aggravated in rats after LPS administration. The above changes showed that the pathological changes of lung tissues ware associated with the decreasing percentage of CD4 + T cells as well as the level of the drift from Th1 to Th2, but there was no parallel relationship between them.Conclusion The reduction of Th1 cells and Th2 cells is associated with apoptosis. The level of apoptosis of Th2 cell is lower than that of Th1 cell, which may be one of the causes of Th1/Th2 shift.DEX can adjust the ratio of Th1/Th2 to a normal level by regulating inflammatory reaction. Apoptosis of CD4 + T cells and the shift of T cell

关 键 词：凋亡 TH1/TH2漂移 急性肺损伤 内毒素 地塞米松 

分 类 号：R563[医药卫生—呼吸系统]