角质细胞生长因子在内毒素耐受大鼠肺部表达的变化

Pulmonary Keratinocyte Growth Factor Production during LPS-Initiated Lung Inflammation in Endotoxin Tolerant Rats

目的:研究内毒素血症时内毒素耐受大鼠肺部角质细胞生长因子(KGF)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0．6 mg／kg连续4d建立内毒素耐受模型。第5天腹腔注射6 mg／kg。各组按注射大剂量LPS前(0 h)．注射后2、6、24 h分为4小组,n=5。用ELISA测定肺组织匀浆中 KGF的浓度。用SPSS 11．5医学统计软件分析数据。结果:反复小剂量LPS注射后,ET组较NC组肺组织KGF蛋白水平上调,分别为(35．6±5．0)pg／ml和(24．2±5．3)pg／ml,P=0．009;给药后两组均下降,然而ET组下降幅度较小,而且各时间点KGF浓度均高于NC组,其中2 h和6 h有显著差异。结论:内毒素耐受有利于减轻大剂量内毒素引起的肺部 KGF蛋白表达抑制,这可能和其肺损伤程度减轻有关。

Objective：To study the protein production of keratinocyte growth factor （KGF） in endotoxin tolerant rats. Methods： Forty Sprague--Dawley male rats were randomized into endotoxin tolerance （ET） group and normal comrol （NC） group. Endotoxin tolerance was induced by four daily intraperitoneal injections of 0. 6 mg/kg/day Escherichia coll LPS （serotype 055： B5）. 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 Lung tissue was collected before and 2, 6, 24 hours after the high dose injection of LPS （five rats for each time point）. The protein production of KGF was measured by ELISA. Software SPSS 11.5 was utilized for statistical analysis. Results： Before high dose LPS challenge, KGF production in lung tissue was higher in ET group （35.6 ＋ 5.0） pg/ml than in NC group （24. 2 ＋ 5.3） pg/ml, P=0. 009. After the challenge of high dose LPS, the level of KGF rapidly decreased in NC group, reaching its nadir with （5.0 ＋ 1.4） pg/ml at 6 hours after injection （P=0. 001）. As contrasted, the KGF level in ET rats decreased more slowly and the value was significantly higher than that of NC group at 2 h and 6 h. Conclusion： The induction of endotoxin tolerance is associated with a higher level of KGF in lung tissue, which might be protective against severe lung injury initiated by endotoxemia.