内毒素耐受对肺部E选择素和血管细胞间黏附分子1表达的影响  

Endotoxin tolerance inhibits lipopolysaccharide-induced early pulmonary expression of E-selectin and vascular cell adhesion molecules-1 in rats

作　　者：张静 瞿介明[2] 何礼贤[1] 徐金富[1] 李倬哲[1] 

机构地区：[1]复旦大学附属中山医院呼吸科,上海200032 [2]复旦大学附属华东医院呼吸科

出　　处：《中国呼吸与危重监护杂志》2007年第5期344-347,共4页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：上海市科技发展基础研究项目(编号:01JC14016);上海市2001年度曙光学者计划项目(编号:01SG06);2006年复旦大学青年基金项目(编号:Z-16/36)

摘　　要：目的观察内毒素血症时内毒素耐受(ET)大鼠血清和肺部E选择素与血管细胞间黏附分子1(VCAM-1)的动态变化,及其与非内毒素耐受(non-ET)大鼠的异同。方法ET组SD大鼠腹腔注射脂多糖(LPS)0.6mg.kg-1.d-1,连续4d,建立ET模型。第5d两组大鼠均腹腔注射大剂量(6mg/kg)LPS诱导全身及肺部炎症反应。采用双抗体夹心酶联免疫吸附法测定注射大剂量LPS前(0h),以及注射后1,2,6和24h的血清、支气管肺泡灌洗液(BALF)及肺组织匀浆中E选择素与VCAM-1的蛋白水平。结果ET组和non-ET组在注射大剂量LPS后血清E选择素和VCAM-1的表达无显著差异(P>0.05)。ET组BALF中的E选择素的上升滞后于non-ET组:E选择素在non-ET组接受大剂量LPS后1h即出现明显升高,之后下降;ET组高峰则在6h;1h时ET组明显低于non-ET组[(36.66±10.24)pg/mL比(89.72±16.66)pg/mL,P<0.001]。肺组织E选择素表达与BALF中的变化趋势相似。BALF中的VCAM-1表达在ET组中0,1,2和6h四个时间点均低于non-ET组,其中1h时间点差异显著(P<0.01)。在2和6h时non-ET组肺组织的VCAM-1急剧升高,而ET组几乎无上升,non-ET组6h时较ET组明显升高(P<0.05)。结论在内毒素耐受状态下,大剂量LPS腹腔注射所致的肺部E选择素和VCAM-1早期表达被阻滞。Objective It has been observed that endotoxin tolerance can block the pulmonary leuckocyte influx and sequestration in endotoxemia. In this study, the systemic and pulmonary expression of Eselectin and vascular cell adhesion molecules-1 （VCAM-1） in endotoxin tolerant rots was assessed to explain the possible mechanism of this phenomenon. Methods Endotoxin tolerance was reproduced by four consecutive daily intraperitoneal injections of 0.6 mg/kg of Escherichia coli 055：B5 lipopolysaccharide（LPS）. On the 5th day,6 mg/kg of LPS was injected to induce lung inflammation. The protein concentrations of E-selectin and VCAM-1 in plasma, bronchial alveolar lavage fluid（BALF） and lung tissue homogenate were analysed and compared with the non-endotoxin tolerant rats before and 1,2,6,24 h after high dose LPS challenge. Results Histopathological examination showed that the acute neutrophilic pulmonary inflammation initiated by LPS was alleviated in the endotoxin tolerant rats. After the high dose LPS challenge,the increases of both E-selectin and VCAM-1 production in BALF were delayed in the tolerant rats. The expression at 1 h of the tolerant group was significantly lower than that of the control group [ （ 33.66 ± 10.24 ） pg/mL vs （ 89.72 ± 16.66） pg/mL （ P 〈 0.001 ） and （4.92 ± 0.31 ）ng/mL vs （5.76 ± 0.41 ） ng/mL（ P 〈 0.01 ）, respectively]. The increase of E-selectin in lung tissue was retarded in the tolerant group than that in the control group, which was similar to that in BALF. Compared to the control rots,the rapid and substantial increase of VCAM-1 expression in lung tissue was almost blocked in the tolerant rats. There was a rapid elevation in serum concentration of E-selection and VCAM- 1 in both groups, although the extent of increase was smaller and the restoration was quicker in the tolerant group. Conclusion These data suggest that the early rapid increase of pulmonary expression of E-selectin and VCAM-1 is vanished in endotoxin tolerant rats.

关 键 词：内毒素耐受 内毒素血症 E选择素 血管细胞间黏附分子1 肺 大鼠 

分 类 号：R563[医药卫生—呼吸系统]