TNF-α和CINC在内毒素耐受大鼠肺部炎症中的动态变化  

Pulmonary TNF-α Production and CINC mRNA Expression During LPS-initiated Lung Inflammation in Endotoxin Tolerant Rats

作　　者：张静 瞿介明[1] 何礼贤[1] 潘珏[1] 欧周罗[2] 张杏怡[1] 陈雪华[1] 

机构地区：[1]复旦大学附属中山医院呼吸科,上海200032 [2]复旦大学附属肿瘤医院中心实验室,上海200032

出　　处：《复旦学报（医学版）》2004年第2期138-141,共4页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金 ( 3 0 3 713 4);上海市科技发展基础研究项目 ( 0 1JC14 0 16);上海市 2 0 0 1年度曙光学者计划项目 ( 0 1SG0 6);上海市百人计划资助课题 ( 98BR0 3 0 )

摘　　要：目的　研究内毒素血症时内毒素耐受大鼠肺部肿瘤坏死因子 -α(TNF α)和细胞因子诱导的中性粒细胞趋化物 (CINC)表达的情况。方法　SD大鼠随机分入正常对照组 (NC组 )和内毒素耐受组 (ET组 )。腹腔注射脂多糖 (LPS) ,每日 0 .6mg/kg连续 4d建立内毒素耐受模型。第 5天腹腔注射 6mg/kg。各组按注射大剂量LPS前 (0h) ,注射后 2、6、2 4、4 8、72h分为 6小组 ,n =6。用ELISA测定BALFTNF α。用RT PCR半定量检测肺组织CINCmRNA的表达。用SPSS 10 .0医学统计软件分析数据。结果　NC组注射LPS(6mg/kg)前 ,BALF中有少量TNF α ,肺组织有微量CINCmRNA表达 ;给药后两者均迅速上升 ,前者的高峰为 6h ,(10 .79±3.5 3) μg/L ,P =0 .0 0 1,后者的高峰出现于 2～ 6h(相对值为 1.6左右 ,P <0 .0 0 1) ,持续至 2 4h。而ET组两者均无上升。结论　内毒素耐受时 ,大剂量内毒素引起的肺部炎症反应和肺损伤减轻与肺部TNFPurpose: To study the pulmonary tumor necrosis-alpha (TNF-α) and cytokine-induced neutrophil chemoattractant (CINC) expression in endotoxin tolerant rats. Methods: Seventy-two Sprague-Dawley male rats were randomized into endotoxin tolerance (ET) group and normal control (NC) group. Endotoxin tolerance was induced by four daily intraperitoneal injections of 0.6 mg/kg/day Escherichia coli LPS (serotype 055: 135). NC group received intraperitoneal injections of the same volume saline. On the fifth day, rats were injected with high dose of LPS (6 mg/kg) to induce endotoxemia and lung inflammation. Right lung tissue and bronchoalveolar lavage fluid (BALF) of left lung were collected before and 2,6,24, 48,72 hours after the high dose injection of LPS (six rats for each time point). The protein production of TNF-α in BALF was measured by ELISA, while the mRNA expression of CINC by RT-PCR. Software SPSS 10.0 was utilized for statistical analysis. Results: Before high dose LPS challenge, TNF-α production in BALF and CINC mRNA expression in lung tissue was little in both groups. In NC group, the level of TNF-αand CINC mRNA both rapidly increased after challenge. TNF-α reached its peak at 6 hours after injection, with the level achieved (10.79 ± 3.53) μg/L (P = 0.001), while CINC mRNA showed a peak between 2 and 6 hours, with the comparative value of about 1.6 (P < .001). As contrasted, the TNF-α level in BALF and CINC mRNA expression of lung tissue in ET rats were not elevated. Conclusions: The induction of endotoxin tolerance is associated with a profoundly low level of TNF-α in BALF and CINC mRNA in lung tissue when challenged with high dose LPS.

关 键 词：TNF-Α CINC 内毒素耐受 大鼠 肺部炎症 动态变化 

分 类 号：R563.1[医药卫生—呼吸系统]