内毒素性肺损伤外周血中性粒细胞CD11b表达的意义

Predictive value of CD11b expression of polymorphonuclear leukocyte in peripheral in rats with acute lung injury induced by endotoxin

目的:探讨内毒素血症大鼠外周血中性粒细胞(PMN)表面CD11b表达与内毒素性肺损伤的关系。方法:大肠杆菌E.Coli O_(111)B_4 4mg/kg尾静脉注射制备大鼠内毒素血症动物模型。112只大鼠随机分为对照组(静脉注射等量生理盐水)及内毒素注射后1h组、2h组、4h组、8h组、12h组、24h组,每组16只动物。在相应时间点放血处死动物,分别取股静脉血、肺组织及进行支气管肺泡灌洗,测定肺组织湿/干重(W/D)比值、肺组织髓过氧化物酶(MPO)活性和支气管肺泡灌洗液(BALF)总蛋白定量等肺损伤指标。流式细胞仪测定外周血PMN表面CD11b表达。另取16只大鼠,内毒素注射后2h时测定外周血PMN表面CD11b表达,24h时放血处死,测定上述指标。结果:①大鼠内毒素血症可以造成明显的急性肺损伤,表现为肺组织W/D比值、MPO活性和BALF总蛋白明显增高,分别在2h、8h和2h显著高于对照组(P<0.05或P<0.01),峰值分别出现在内毒素注射后12h、24h和12h;②大鼠内毒素性肺损伤时,外周血PMN表面CD11b表达水平在早期(1h)明显升高(与对照组比较,P<0.05),在2h达到峰值,之后逐渐降低;③外周血CD11b表达峰值明显早于肺组织W/D比、MPO和BALF总蛋白等肺损伤指标的峰值出现时间;④同一动物2h时外周血PMN表面CD11b的表达水平与其24 h时肺组织W/D比、MPO和BALF总蛋白含量呈显著正相关(r分别为0.78、0.77和0.73,P<0.05)。结论:内毒素性肺损伤中,外周血CD11b表达升高可能有助于内毒素性肺损伤的早期诊断,并可能预示以后的肺损伤程度。

Objective： To investigate the CDllb expression of polymorphonuclear leukocyte （PMN） in endotoxin-induced acute lung injury and the relationship between the expression and the lung injury. Methods： The experiment consisted of two parts. In the first part, E. coli endotoxin O111B4 was injected intravenously to rats to induce acute lung injury. Rats were killed 1, 2, 4, 8, 12, 24 hours after endotoxin injection,with 16 rats at each time point. Sixteen rats without endotoxin injection served as control group. The positive expression of CDllb in PMN was measured by flow cytometry （FCM） in all rats, and the wet to dry ratio （W/D） of the lung, the myeloperoxidase （MPO） level of lung tissue, and the total protein content of bronchoalveolar lavage fluid （BALF） were measured. In the second part of the experiment, 16 rats were injected with E. coli endotoxin On1 B4, and the CD11b were measured 2 hours after injection, while the W/D of lung tissue, the MPO of lung tissue, and the total protein of BALF were measured 24 hours after the injection. Results： （1） Experimental rats presented the acute lung injury after the injection of E. coli endotoxin O111B4 , in which the W/D and MPO of lung tissue, and total protein in BALF were increase significantly comparing with those of the control group （P〈0.05 or P〈0.01）; they reached the peak value at 12, 24, 12 hours respectively. （2） The CD11b expression of PMN was upregulated 1 hour later in endotoxin-induced acute lung injury, and its peak value occurred at 2 hours （P〈0. 01, comparing with those of the controls）. （3） The peak of CD11b expression of PMN preceded the increase of the W/D and MPO of lung tissue, and total protein of BALF. （4） The CD11b expression of PMN was correlated with the W/D and MPO of lung tissue, and protein of BALF positively, with the correlation coefficients of 0.78 （P=0.02）, 0.77 （P=0. 03） and 0.73 （P=0.04） respectively. Conclusion： The increase in PMN CD11b expression in endotoxemia precedes the endotoxin-induced acute lung injury. The level of PMN CDllb expression may be a predictive marker for the diagnosis and degree of endotoxin-induced acute lung injury.