糖皮质激素对不同诱因急性肺损伤大鼠炎症反应、激素受体水平的影响

Effects of dexamethasone on inflammatory reaction and glucocorticoid receptors level in ALI rats induced by different factors

目的探讨经静脉注射脂多糖(LPS)、向气管内滴入盐酸(HCl)致两种急性肺损伤(ALI)大鼠用糖皮质激素地塞米松(Dex)后其炎症反应、受体机制及对激素反应的差异。方法SD大鼠96只,随机分为6组(每组16只):NS组、LPS组、HCl组、生理盐水(NS)+Dex组、LPS+Dex组、HCl+Dex组,每个组又分为两个亚组:支气管肺泡灌洗组和非灌洗组。检测各组支气管肺泡灌洗液(BALF)中细胞总数、中性粒细胞百分比、巨噬细胞百分比、淋巴细胞百分比、蛋白含量和肺湿/干重比(W/D),比较各组血清和BALF中致炎因子TNF-α、IL-1β和抗炎因子IL-4、IL-10的水平,血清糖皮质激素(GCs)及外周血单个核细胞(PBMC)上的糖皮质激素受体(GR)水平。结果①LPS组、HCl组BALF中细胞总数、中性粒细胞百分比、蛋白含量和肺W/D均高于NS组(P<0.05)。LPS+Dex组巨噬细胞百分比高于LPS组(P<0.05)。②LPS组和HCl组血清和BALF中TNF-α、IL-4、IL-10水平均高于NS组的相应水平(P<0.01)。各组血清中IL-1β的含量均未测出。LPS+Dex组BALF中TNF-α、IL-1β含量低于LPS组的相应水平(P<0.05),而IL-10高于LPS组的相应水平(P<0.01)。③与NS组比较,HCl组PBMC上GR明显下降,而LPS+Dex组GR与GCs含量均高于HCl+Dex组。结论两个模型组在炎症因子水平、糖皮质激素受体水平存在一定的差异,糖皮质激素对LPS所致的ALI有拮抗作用,但对HCl所致ALI作用不明显。

Objective To explore the inflammatory reaction, glucocorticoid receptors（GR） level and the discrepancy of reaction to dexamethasone（Dex） in acid（HCl ） and lipopolysaccharide （LPS）. Methods acute lung imgurgl（ALI） rats induced by hydrochloric Ninety-six SD rats were divided into six groups at random （ n=16 in each group） ： NS group. HCI group. LPS group. NS＋ Dex group. HCI ＋ Dex group and I,PS ＋Dex group. Every group was divided into two subgroups. the bronchoalveloar lavage（BAL） subgroup and no bronchoalveloar lavage（NBAL） subgroup. The total leukocytes. PMN%. macrophage%, lymphocyte%, total protein in BALF and the wet/dry weight of the lung were measured, The concentrations of TNF-α. IL- 1β,IL-4 and IL-10 in serum and BALF.the concentrations of serum cortisol（GCs） and the level of GR in peripheral blood mononuclear cells （PBMC）in every group were compared. Results① In LPS group and HCl group, the total leukocytes. PMN numbers, the protein concentration in the BALF and W/D were higher than those of the control group（ P〈0.05）. Comparing to LPS groups, the percentage of macrophage increased in LPS＋Dex group（ P 〈0. 05）. ②In serum and BALF of both of I.PS group and HCI group,the concentrations of TNF-α. IL-4 and IL-10 were higher than those of the control（ P 〈0. 01）. The content of IL-1β in serum of all the groups was undetected. Comparing to LPS groups, the concentrations of TNF-α and that of IL-16 decreased in LPS＋Dex group（ P〈0. 05）. The concentrations of IL-10 of LPS＋Dex group was higher than that of LPS group（ P 〈0.01）. ③Comparing to NS group, the level of GR in HCI group was remarkably decreased （ P〈0. 05）. GR and GCs in LPS ＋ Dex group were obviously higher than those of HCl＋Dex group（ P （0. 05 ）. Conclusions The inflammatory cytokines in these two models were not consistent. The differences in the efficacy of GCs therapy may be associated with the change of numbers and functions of GR. GCs play an effective role for resisting ALI induced by LPS but not HCI.