输血相关急性肺损伤小鼠模型的建立  

The establishment of a mouse model for transfusion-related acute lung injury

作　　者：王蕾[1,2] 张会强[3] 王玥[2] 吴涛[2] 付秋霞[2] 詹林盛[1,2] 

机构地区：[1]广西医科大学,广西南宁530021 [2]军事医学科学院野战输血研究所,北京100850 [3]解放军第307医院乳腺肿瘤科

出　　处：《中国输血杂志》2016年第3期255-259,共5页Chinese Journal of Blood Transfusion

基　　金：北京市科学技术委员会重点实验室课题(#Z141102004414034)

摘　　要：目的探索建立输血相关急性肺损伤(TRALI)小鼠模型。方法雄性Balb/c小鼠随机分为5组(分别命名为A、B、C、D及E组),前4组小鼠5只/组,E组15只/组。E组(TRALI模型组):每只小鼠腹腔注射1 mg/m L脂多糖(LPS)预处理,注射剂量为0.1 mg/(kg·只),24 h后尾静脉注射1 mg/m L H2Kd单克隆抗体,注射剂量为2.25mg/(kg·只),建立TRALI小鼠模型;其余均为对照组,其中A为空白对照组,B为注射LPS组,C为注射LPS及24 h后注射生理盐水(NS)组,D为注射H2Kd单克隆抗体组。分析各组小鼠肺组织病理、肺湿重/干重比、直肠温度、死亡率等指标,建立TRALI小鼠模型,并以此为基础,对阿司匹林(ASA)干预小鼠TRALI的效果做验证。结果与对照组相比,TRALI模型组小鼠2 h的直肠温度(31.060±0.472)℃,明显低于其他各对照组小鼠(P<0.01),肺湿重/干重比为7.642±1.309,则较其他各组明显增加(P<0.01);TRALI模型组小鼠肺组织出现肺泡间隔增厚,肺泡壁断裂,肺泡内纤维蛋白浸润等病理变化,符合TRALI急性肺损伤典型的症状及体征;在ASA干预后2 h,TRALI小鼠死亡率为0,肺水肿明显减轻(P<0.01)。结论成功建立了TRALI小鼠模型,该模型能够模拟TRALI的临床表现,可重复性强,稳定性好,有助于解释TRALI病理过程、探索TRALI的救治措施。Objective To establish a mouse model ibr transfusion-related acute lung injury. Methods Male Balb / c mice were randomly divided into five groups （ named A, B, C, D and E） ： （A） Normal mice, （B） mice given i.p. LPS （0. 1 mg/kg）, （C） mice given i. p. LPS （0, 1 mg/kg） and i. v. NS via the tail vein at 24 hours after injection, （D） mice given i. v. MHC I mAb （ H2Ka ,2. 25 mg/kg） via the tail vein and （E） TRALI mice. There were 5 mice in the groups A, B, C, D and 15 mice in the group E. To induce TRALI, mice were first challenged with i. p. lipopolysaccharide （LPS,0. 1 mg/kg）, and then transfused with H2Kd （2. 25 mg/kg） via the tail vein. Various physiologic measurements were then per- formed at the indicated time points. The lung pathological changes, wet to dry weight ratio change, rectal temperature and survival rate were studied respectively. Based on this model, the effect of aspirin treatment on TRALI was also explored. Re- sults After injection of MHC I mAb 2 hours, compared with other groups, the mouse challenged with both LPS and MHC I mAb showed dropped rectal temperature [ （ 31.060 ± 0. 472 ） ℃, P 〈 0. 01 ], increased lung wet to dry weight ratio （7. 642±1. 309, P 〈 0. 01 ）. The typical pathological changes of alveolar septal thickening, alveolar wall rupture, alveolar fibrin infiltration, indicating that the mice model of TRALI was successfully established. Treatment with aspirin could allevi- ate TRALI, which showed no mortality and significant reduced wet to dry weight ratio （P 〈0. 01 vs other groups）. Conclu- sion In this study we have developed an in vivo mouse model of TRALI in a clinically relevant using LPS in combination with MHC I mAb,which provides a stable platform for the study both on the pathogenesis and treatment of TRALI.

关 键 词：输血相关急性肺损伤 动物模型 肺组织 病理变化 直肠温度 肺湿重/干重 阿司匹林 小鼠 

分 类 号：R457.13[医药卫生—治疗学] R563.8[医药卫生—临床医学]