摘要
目的 探讨E选择素在新生儿急性肺损伤（acute lung injury,ALI）发病中的作用及其意义.方法 选择6～7日龄新生Sprague Dawley大鼠90只,随机分为对照组10只、ALI组80只,ALI组再分为0.5、1、2、3、4、8、12 h和24h亚组,每个亚组10只.ALI组新生大鼠腹腔注射脂多糖（lipopolysaccharide,LPS）4 mg/kg制备新生大鼠ALI模型;对照组注射等体积生理盐水.ALI组新生大鼠分别在腹腔注射LPS后0.5、1、2、3、4、8、12、24 h,对照组在腹腔注射生理盐水后4h断头处死,检测血清可溶性E选择素含量,观察肺组织病理改变,测定肺组织湿重/干重比值及肺组织E选择素的表达.结果 ALI组新生大鼠肺组织血管内皮细胞可见大量E选择素强阳性表达细胞,对照组肺组织血管内皮细胞仅见极少E选择素弱阳性表达细胞.ALI组新生大鼠腹腔注射LPS 0.5 h后肺组织湿重/干重比值即开始逐渐升高,8h达高峰,之后开始下降,4～12h各时间点湿重/干重比值均高于对照组,差异有统计学意义（P＜0.05）.显微图像分析显示,ALI组新生大鼠腹腔注射LPS后肺组织E选择素平均光密度值明显高于对照组,其中2 ～8 h ALI组平均光密度值与对照组比较差异有统计学意义[2 h：（0.36±0.09）,3 h：（0.38±0.01）,4 h：（0.44 ±0.06）,8 h：（0.30±0.09）,对照组：（0.24±0.01）,P＜0.05].ALI组新生大鼠腹腔注射LPS后血清可溶性E选择素水平逐渐升高,2h达峰值,此后逐渐降低,在2～8h时间点均明显高于对照组,差异有统计学意义（P＜0.05）.血清可溶性E选择素水平随肺组织E选择素表达增加而升高,成正相关（r =0.730,P＜0.01）.结论 肺组织E选择素表达增强及血清可溶性E选择素水平升高可反映全身炎症反应过程中肺血管内皮细胞损伤.
Objective To investigate the role and significance of E selectin in the pathogenesis of neonatal acute lung injury （ALI）.Method Ninety neonatal Sprague Dawley （SD） rats （6 or 7 days after birth） were randomly assigned to the control group （n =10） and ALI group （n =80）.The rats in the ALI group received intraperitoneal injection of lipopolysaccharide （LPS） at dose of 4 mg/kg and they were divided into eight subgroups with 10 rats in each group according to different sacrifice time （0.5 h,1 h,2 h,3 h,4 h,8 h,12 h and 24 h after injection）.Rats in the control group were injected intraperitoneally the same volume of normal saline and they were sacrificed at 4 hours after injection.Expression of the E-selectin in lung tissue was detected dynamically by immunohistochemistry and the serum soluble endothelial selectin （sE-selection） was detected by enzyme-linked immunosorbent assay （ELISA）.The pathological changes of the lung tissue and the wet/dry lung weight ratio （W/D ratio） were recorded.Result The strong expression of a large number of E-selectin was detected in the vascular endothelial cells of the lung tissue in the ALI group,while only moderate expression of E-selection was observed in the control group.The W/D ratio in the ALI group gradually increased from 0.5 h after intraperitoneal injection of LPS,reached the peak at 8 h,and then began to decline.The ratio was significantly higher in the ALI group than that of the control group from 4 to 12 h after injection （P 〈 0.05）.The mean optical density of E-selectin in lung tissue of ALI group was also higher than that of the control group and the average optical density of ALI group at 2 h,3 h,4 h and 8 h was significantly higher [2 h：（0.36 ±0.09）,3 h：（0.38 ±0.01）,4 h：（0.44 ± 0.06）,8 h：（0.30 ± 0.09）,control group：（0.24 ± 0.01）,P 〈 0.05].The level of serum sE-selectin gradually increased after intraperitoneal injection of LPS,reached the peak at 2 h,and then decreased gradually.The level of sE selection was significantly higher than that of the control group at the point of 2 h,3 h,4 h and 8 h （P 〈 0.05）.The level of serum sE-selectin increased along with the expression of E-selectin in lung tissues,and they were positively correlated （r =0.730,P 〈 0.01）.Conclusion The increased expression of E-selectin and the elevation of serum sE-selectin level may reflect the injury of pulmonary vascular endothelial cells induced by systemic inflammatory response.
