整合素介导的肝素结合蛋白在肺损伤模型中的作用  

The role of integrin involved heparin-binding protein secretion in acute lung injury

作　　者：刘杨[1] 马少林[1] 王学斌[1] 徐玮[1] 章守琴[2] 张翔宇[2] Liu Yang;Ma Shaolin;Wang Xuebin;Xu Wei;Zhang Shouqin;Zhang Xiangyu(Intensive Care Unit, East Hospital Tongji University School of Medicine, Shanghai 200120, China （Liu Y, Ma SL, Wang XB, Xu W;Department of Critical Care, Tenth People＇s Hospital of Tongji University, Shanghai 200072, China （Zhang SQ, Zhang XY)

机构地区：[1]同济大学附属东方医院中心监护室,上海200120 [2]同济大学附属上海第十人民医院重症医学科,上海200072

出　　处：《中华急诊医学杂志》2018年第7期764-768,共5页Chinese Journal of Emergency Medicine

基　　金：上海市卫生和计划生育委员会科研课题（20144Y0231）

摘　　要：目的探讨在肺损伤病理过程中，肝素结合蛋白的释放与中性粒细胞表面的β2整合素及其与肺损伤的关系。方法30只C57BL/6小鼠来自同济大学实验动物中心，随机（随机数字法）分为对照组、结肠穿刺肺损伤组（CLP组）和抗体处理组。CLP组和抗体处理组使用结肠穿刺法制作急性肺损伤模型，对照组给予假手术处理。抗体处理组予以造模前注射CD18单抗抑制β2整合素功能。制模24h后小鼠取肺组织，HE染色观察肺组织病理学改变，Smith评分法评估肺损伤程度，行肺湿干比测量，肺泡灌洗液（BALF）行蛋白水平测定，酶联免疫吸附法检测小鼠外周血肝素结合蛋白水平，流式细胞术测量中性粒细胞表面β2整合素表达。各组水平差异比较采用t检验，Pearson法分析肝素结合蛋白与β2整合素和肺损伤指标的相关性。结果与对照组比较，CLP组动物肺Smith评分（t=10.607,P〈0.01）、肺湿干比（t=3.968,P=0.001）和BALF蛋白水平（t=4.331, P〈0.01）等肺损伤指标均明显升高，同时肝素结合蛋白水平（t=3.515,P=0.002）及β2整合素（t=4.816,P〈0.01）差异有统计学意义。而抗体处理组动物肺smith评分（t=2.307,P=0.033）、肺湿干比（t=3.080,P=0.006）和BALF蛋白水平（t=2.484,P=0.023）均较CLP组有降低，肝素结合蛋白水平也有显著降低（t=2.218,P=0.046）。就CLP组和抗体处理组动物进行相关性分析，其肝素结合蛋白水平与肺湿干比（r=0.527,P=0.017）及BALF蛋白均有明显相关性（r=0.508,P=0.022）,HBP水平与β2整合素水平也有明显相关（r=0.674,P=0.001）。结论肝素结合蛋白和β2整合素均参与了肺损伤的病理过程，其中肝素结合蛋白的水平与肺损伤严重程度相关。β2整合素与肝素结合蛋白的释放有关，抑制β2整合素功能可降低肝素结合蛋白水平，同时减轻肺损伤。Objective To study the relationship between heparin-binding protein（HBP） and β2 integrin on the surface of neutrophil in acute lung injury. Methods A total of 30 mice from animal center of Tongji University were divided into control group, CLP group and antibody-treatment group by random number method. Acute lung injury animal model was established by cecal Ligation and puncture in the mice of CLP group and antibody-treatment group. Sham operations were performed on the mice in control group. Mice in antibody-treatment group received anti-CD 18 antibody injected via tail vein 30 min before establishing acute lung injury animal model. Twenty-four hours after operation, mice were sacrificed and lung tissue was taken. After HE staining, lung injury were evaluated by Smith score. Lung tissue wet/dry weight ratio, BALF protein level, plasma HBP level and β2 integrin on neutrophil were measured. T test were used to compare the difference among groups. Pearson correlation was used to study the correlation between HBP, integrin and lung injury index. Results Compared with control group, mice in CLP group had higher Smith score（t=10.607, P〈0.01）, lung wet/dry ratio（t=3.968, P=0.001）,BALF protein level（t=4.331, P〈0.01） and as well as higher plasma HBP（t=3.515, P=-0.002） and β2 integrin（t=-4.816, P〈0.01） level. After CD18 antibody treatment, anti-treat group mice had lower Smith score （t=2.307, P=0.033）, lung wet/dry ratio（t=3.080, P=0.006）,BALF protein level（t=2.484, P=-0.023） and as well as higher plasma HBP level（t=2.218, P=0.046） than mice in CLP group. Pearson correlation analysis showed HBP had obvious correlation with wet/dry ratio（r=0.527, P=-0.017）,BALF protein（r=0.508, P=-0.022） and as well as β2 integrin（r=0.674, P=-0.001）. Conclusions Both HBP and β2 integrin involved in the lung injury pathogenesis. HBP level is interrelated with the severity of lung injury. The β2 integrin is associated with the release of HBP by neutrophil. Inhabiting the functio

关 键 词：急性呼吸窘迫综合征 急性肺损伤 肝素结合蛋白 Β2整合素 中性粒细胞 

分 类 号：R-332[医药卫生] R563.8