【摘要】 目的:制作急性肺损伤(ALI)模型并检测细胞间黏附分子-1(ICAM-1)、E-选择素和P-选择素在实验兔血清、肺组织及支气管肺泡灌洗液(BALF)中的变化情况以探讨三者在ALI中的作用并观察联合应用氨溴索与小剂量肝素对其的影响。方法:24只健康兔随机分成3组:对照组(NC组),油酸损伤组(OA组),氨溴索+小剂量肝素治疗组(AH组)。采用耳缘静脉法静注油酸复制兔ALI模型,检测各组动脉氧分压(PaO2),ELISA法检测ICAM-1和E-选择素,TUNEL法检测凋亡指数(AI),免疫组化检测P-选择素,电镜观察肺组织超微结构变化并测定湿干重比值(W/D)。结果:与NC组比较,OA组和AH组PaO2显著降低(P<0.01),但AH组显著高于OA组(P<0.01);ICAM-1、E-选择素的浓度(血清、肺组织及BALF中)、肺组织AI和W/D升高(P<0.05或P<0.01),但AH组低于OA组(P<0.05或P<0.01)。与同组给予治疗药物前0 h比较,NC组无差异(P>0.05),OA组各时点PaO2显著降低(P<0.01),ICAM-1和E-选择素浓度显著升高(P<0.01),AH组各时点PaO2降低(P<0.05)、ICAM-1和E-选择素浓度升高(P<0.05)。肺组织中P-选择素在OA组表达较为广泛:主要为炎症细胞、毛细血管的内皮细胞和血管内的血浆等,NC组呈低水平表达,AH组的表达介于两者之间。细胞凋亡以OA组最为明显,NC组未见细胞凋亡或偶有凋亡,AH组凋亡的细胞明显比OA组减少。结论:在OA致ALI时,ICAM-1、E-选择素和P-选择素明显增高,参与了ALI的发生、发展;联合应用氨溴索与小剂量肝素可以降低ICAM-1、E-选择素和P-选择素的水平,减轻肺脏细胞的损伤、改善肺通气和换气功能、减轻肺水肿,从而发挥对ALI的防治作用。更多还原

【Abstract】 AIM:To study the production of intercellular adhesion molecule-1(ICAM-1),E-selectin and P-selectin in serum,lung tissues and bronchoalveolar lavage fluid(BALF)of acute lung injury(ALI) model and to observe the effects of ambroxol combined with low-dose heparin on the changes of the 3 factors above.METHODS:Twenty-four healthy rabbits were randomly divided into 3 groups:normal saline control group(NC),oleic acid injury group(OA),ambroxol+ heparin treatment group(AH).The rabbit ALI model was induced by oleic acid injection through auricular vein.Partial pressure of O2 in artery(PaO2) was analyzed.The concentrations of ICAM-1 and E-selectin were detected by ELISA.The apoptosis index(AI) was measured by TUNEL method.The expression of P-selectin was determined by immunohistochemical method.The ultrastructural changes of the lung tissues were observed under electron microscope,and the lung wet/dry ratio(W/D) was calculated.RESULTS:PaO2 in AH group and OA group was significantly lower(P<0.01) than that in NC group,and PaO2 in AH group was significantly higher than that in OA group(P<0.01).The concentrations of ICAM-1 and E-selectin in serum,lung tissues and BALF,and AI and W/D in lung tissues in AH group were higher(P<0.05 or P<0.01) than those in NC group,and was lower than those in OA group(P<0.05 or P<0.01).In NC group,no significant change of the above parameters at all time points was observed(P>0.05).In OA group,PaO2 was significantly decreased(P<0.01) with the pathological process developed,and the concentrations of ICAM-1 and E-selectin were significantly increased.In AH group,PaO2 was decreased(P<0.05),and the concentrations of ICAM-1 and E-selectin were increased with the process of ALI developed.The P-selectin expression in lung tissues of OA group was distributed mainly in inflammatory cells,capillary endothelial cells and plasma.From low to high levels,the order was NC group < AH group < OA group in the expression of P-selectin.The most obvious apoptosis was observed in OA group.No apoptosis or occasional positive cells were found in NC group.The apoptotic rate in AH group was significantly reduced compared with that in OA group.CONCLUSION:In ALI induced by OA,ICAM-1,E-selectin and P-selectin are significantly increased and are involved in the occurrence and development of ALI.Ambroxol combined with low-dose heparin reduces the levels of ICAM-1,E-selectin and P-selectin,the pulmonary edema and the lung injury,improves pulmonary functions,and plays an important role in the prevention and treatment of acute lung injury.更多还原