内毒素预处理对兔肝脏缺血-再灌注后肺损伤的保护效应  

The protective effect of endotoxin pretreatment on lung injury induced by hepatic ischemia reperfusion in rabbits

作　　者：葛云洁[1] 王野 张淑立[1] 赵伟业[1] 鲁德忱 玛黎清[1] 

机构地区：[1]青岛市立医院呼吸科,山东青岛266011 [2]青岛海慈医院肝胆外科

出　　处：《中华急诊医学杂志》2008年第11期1167-1170,共4页Chinese Journal of Emergency Medicine

摘　　要：目的探讨内毒素预处理对肝脏缺血-再灌注后肺损伤的影响及机制。方法将48只新两兰大白兔随机分为一般对照组（C一般组）和预处理对照组（C预处理组），缺血-再灌注组（IR组）和预处理再灌注组（LPS＋IR组），每组12只。C一般组仪行手术解剖；C预处理组手术解剖前3d分别经腹腔注射0．5、0．5和1．0mg／kg脂多糖（LPS）进行内毒素预处理；IR组夹闭肝门30min，再灌注4h，进行肝脏缺血-再灌注；LPS＋IR组行内毒素预处理后再行肝脏缺血．再灌注。检测各组再灌注后4h血清内毒素、肿瘤坏死因子-α（TNF-α）、肺湿干比、灌洗液蛋白含量、组织匀浆丙二醛（MDA）、超氧化物歧化酶（SOD）、肺损伤率及肺泡巨噬细胞核因子-κB（NF-κB）活性的变化。组间比较采用单因数方差分析。结果C一般组和C预处理组各项检测指标差异无统计学意义（P〉0．05）。LPS＋IR组血清TNF-α[（48．31±5．31）pg／ml vs．（56．47±5．09）pg／ml，P〈0．01]、肺湿干比[（4．98±0．33）vs．（5．22±0．31），P=0．03]、灌洗液蛋白含量[（0．68±0．11）g／L vs．（0．76±0．10）g／L，P=0．04]、MDA[（0．86±0．06）nmol／mg vs．（0．93±0．07）nmol／mg，P=0．02]、肺损伤率[（13．4±4．3）％vs．（17．4±4．1）％，P=0．033及肺泡臣噬细胞NF-κB活性[（5．82±1．12）OD／mm^2 vs．（7．40±1．26）OD／mm^2，P〈0．01]明显低于IR组；同时LPS＋IR组SOD[（90．30±7．38）U／mg vs．（84．44±7．90）U／mg，P=0．04]明显高于IR组。结论内毒素预处理可以减轻肝脏缺血-再灌注后肺损伤，其机制与降低了血清TNF-α产生及抑制肺泡臣噬细胞中NF-κB活化有关。Objective To investigate the effect of endotoxin pretreatment on lung injury induced by hepatic ischemia reperfusion in rabbits and its mechanism. Method Forty-eight New Zealand white rabbits were randomly divided into 4 groups with 12 rabbits each group： routine control group, pretreatment control group, ischemia reperfusion group （1R group）, and pretreatment repeffusion group（ LPS ＋ IR group）. Rabbits of routine control group received operative dissector only,and those of pretreatment control group received pretreatment of daily intraabdominal injection of lipopolysaccharide（0.5,0.5, and 1.0 mg/kg, respectively）in the 3 days before operative dissector. Livers of IR group were rendered and ischemic for 30 minutes, and reperfused for up to 4 hours. Rabbits of LPS ＋ IR group received the pretreatment before hepatic ischemia reperfusion. Four hours after reperfusion, serum endotoxin, tumor necrosis factor-α（TNF-α）, wet/dry ratio and broncho-alveolar lavage fluid protein content of lung, mal- ondialdehyde（MDA） and superoxide dismutase（SOD） in lung homogenate,lung injury ratio,and activity of Nuclear factor-κB（NF-κB） in alveolar macrophage were examined. Differences within the groups were analyzed using One way ANOVA. Results Between the two control groups, there were no significant differences in all indexes （P 〉 0.05）. The TNF-α （48.31 ± 5.31）pg/ml vs. （56.47 ±5.09）pg/ml, P 〈 0.01] ,wet/dry ratio [ （4.98 ± 0.33） vs. （5.22 ± 0.31）, P = 0.03 ], broncho-alveolar lavage fluid protein content [ （0.68 ± 0.11 ） g/L vs. （0.76 ± 0.10）g/L, P = 0.04], MDA[ （0.86 ± 0.06）nmol/mg vs. （0.93 ± 0.07）nmol/mg, P = 0.02] ,lung injury ratio[（13.4±4.3）% vs. （17.4±4.1）%, P = 0.03],and the activity of NF-κB[（5.82± 1.12）OD/mm^2 vs. （7.40 ± 1.26） OD/mm^2, P 〈 0.01 ] in alveolar macrophage of the LPS ＋ IR group were all significantly lower than those of IR group,while the SOD[ （90.30 ±7.38 ）U/mg vs. （84.44± 7.90 ）U/rag, P

关 键 词：内毒素 预处理 肺损伤 肿瘤坏死因子-α 核因子-ΚB 

分 类 号：R285.5[医药卫生—中药学] R563[医药卫生—中医学]