B和T淋巴细胞衰减因子激活在休克／脓毒症诱导的急性肺损伤中的作用  

Role of B and T lymphocyte attenuator activation in shock/sepsis -induced acute lung injury

作　　者：程婷婷[1] 白建文[1] 

机构地区：[1]同济大学附属东方医院急诊内科,上海200120

出　　处：《中国急救医学》2015年第7期646-650,I0003,共6页Chinese Journal of Critical Care Medicine

基　　金：上海市浦东新区卫生和计划生育委员会科技发展专项基金（PW2014D-9）

摘　　要：目的探讨B和T淋巴细胞衰减因子（BandTlymphocyteattenuator，BTLA）激活在休克／脓毒症诱导的急性肺损伤（ALI）中的作用。方法24只雄性C57BL／6小鼠随机平均分为三组：对照组、Au模型组和6A6（BTLA激动性抗体）干预组。采用Westernblot观察对照组和AU模型组肺组织BTLA蛋白的表达变化，并测定和比较三组小鼠支气管肺泡灌洗液蛋白浓度，ELISA方法测定肺组织促炎症细胞因子、趋化因子水平及肺组织髓过氧化物酶活性，TUNEL染色评估肺组织细胞凋亡情况；肺组织切片HE染色了解肺组织病理学改变。另外45只小鼠随机平均分为如上三组观察10d生存率。结果BTLA在Au模型组肺组织中表达较对照组明显升高。与Au模型组比较，6A6干预组小鼠支气管肺泡灌洗液蛋白浓度升高，肺部TNF—α和MIP-2、MCP-1水平升高，肺组织MPO活性增加（P均〈0．05）。TUNEL染色显示，6A6干预组小鼠肺细胞凋亡较Au模型组增加。HE染色显示，6A6干预组较Au模型组小鼠肺组织病理学形态损伤加重。6A6干预组较Au模型组小鼠死亡率显著升高。结论BTLA在休克／脓毒症诱导的ALI肺组织中表达升高。BTLA激活使脓毒症诱导的Au小鼠肺通透性增高，肺部炎症因子和趋化因子水平升高，肺部中性粒细胞募集增加，肺细胞凋亡增加，肺组织病理学形态损伤加重，导致ALI小鼠死亡率增加。Objective The purpose of this study is to assess the effect of B and T lymphocyte attenuator activation in shock/sepsis - induced acute lung injury（ALl）. Methods Twenty - four mice were randomly divided into three groups： control group, ALI group, and ALI＋ 6A6 （ agonistic anti - BTLA antibody） treated group. Expression of BTLA in lung tissue was determined by Western blotting. Bronchoalveolar lavage fluid （BALF） protein concentration and lung myeloperoxidase （MPO） activity was determined. Pro- inflammatory cytokine and chemokine levels were detected by ELISA. Lung cell apoptosis and histology study were processed by Tunel staining and HE staining. Another 45 mice were randomly divided into three groups as above, and used for survival study. Results BTLA expression elevated significantly in lung tissue in ALI group compared to control group. BALF protein concentration, pro - inflammatory eytokine （ TNF - α） and chemokine （ MIP - 2, MCP - 1 ） levels, as well as MPO activity in lung were increased significantly （ P 〈 0.05 ） in ALI ＋ 6A6 treated group compared to ALI group. Enhanced lung apoptosis by Tunel staining and pathologic injuryby HE staining were observed in ALI＋ 6A6 treated group. And the mortality of ALI＋ 6A6 treated mice was elevated significantly compared to ALI mice. Conclusion BTLA activation induces higher lung tissuepermeability, elevated lung inflammatory cytokine and chemokine levels, more neutrophils recruited into lung, as well as enhanced lung apoptosis and pathologic injury in lung during sepsis induced ALI. Activation of BTLA increased the mortality of sepsis - induced ALI mice.

关 键 词：B和T淋巴细胞衰减因子 急性呼吸窘迫综合征 全身炎症反应综合征 免疫调节 

分 类 号：R631.4[医药卫生—外科学]