创伤性ARDS时COX-2调控PMN凋亡的实验研究  

Cyclooxygenase-2 Modulation of Apoptosis of Polymorphonuclear Neutrophil in Traumatic Acute Respiratory Distress Syndrome

作　　者：张金洲[1] 王文[2] 陈文生[1] 朱海龙[1] 孙国成[1] 顾春虎[1] 陈涛[1] 刘维永[1] 易定华[1] 

机构地区：[1]第四军医大学西京医院心血管外科,710032 [2]第四军医大学西京医院中医科,710032

出　　处：《美中国际创伤杂志》2007年第3期8-11,共4页U.S.Chinese International Journal of Traumatology

摘　　要：目的：探究创伤性ARDS时COX-2是否调控了PMN凋亡。方法：本研究由动物实验和细胞实验组成。应用严重胸部钝性撞击伤制造新西兰白兔ARDS模型，观察伤后肺组织COX-2蛋白活性与支气管肺泡灌洗液PMN凋亡改变。分离培养正常PMN，分别给与支气管肺泡灌洗液和NS398＋支气管肺泡灌洗液，观察粒细胞COX-2mRNA表达与PMN凋亡。结果：动物实验中，伤后12小时支气管肺泡灌洗液PMN凋亡明显降低，COX-2活性在伤后呈上升趋势，COX-2活性和PMN凋亡之间存在明显的相关性（γ=0．75，P〈0．01）。离体实验中，与DMEM组相比，BALF和NS398组PMN凋亡明显降低（P〈0．01）。BALF组PMN凋亡明显低于NS398组（P〈0．01）。BALF组COX-2mRNA表达明显高于DMEM组（P〈0．01）。与BALF相比，NS398组COX-2mRNA表达明显降低（P〈0．01），但仍高于DMEM组fP〈0．01）。结论：严重胸部钝性伤后肺内COX-2表达增加抑制了伤后ARDS发病PMN的凋亡。Objective： To verify whether cyclooxygenase-2 （COX-2） regulates apoptosis of polymorphonuclear neutrophil （PMN） in traumatic ARDS. Methods： The study consisted of vitro and vivo two parts. Experimental ARDS was established in New Zealand rabbits by blunt chest trauma, and a correlation analysis of COX-2 immunohisto- chemical staining in lung tissue and PMN apoptosis in bronchoalveolar lavage fluid （BALF） was performed. Apoptosis was measured by flow cytometric analysis of annexin V and propidium iodide dual staining. As an in vitro correlate,normal PMN were treated with BALF from injured lung （BALF ARDS） in the presence or absence of the COX-2 inhibitor,NS398, COX-2 mRNA levels and PMN apoptosis were then measured. Results： In animal experiments,PMN apoptosis was significantly decreased in BALF at 12h after injury. In contrast,COX-2 expression was significantly increased after injury. COX-2 protein expression and PMN apoptosis exhibited a strong inverse correlation （γ=-0.64,P〈0.01）. In vitro experiments,compared with DMEM group apoptosis of normal PMN was significantly decreased in BALF and NS398 group （P〈0.01）,and BALF group was lower than NS398 group. COX-2 mRNA levels increased significantly in BALF group than DMEM group and NS398 group （P〈0.01）,but NS398 group was higher than DMEM group（P〈0.01）. Conclusion： Up-regulation of intrapulmonary COX-2 expression contributes to suppression of PMN apoptosis in traumatic ARDS.

关 键 词：急性呼吸窘迫综合症 环氧合酶2 中性粒细胞 凋亡 

分 类 号：R563.8[医药卫生—呼吸系统]