双重打击急性肺损伤大鼠激素受体mRNA水平及激素干预效果研究

目的 探讨尾静脉注射脂多糖(lipopolysaccharide,LPS)的一次打击及LPS尾静脉注射后盐酸(HCI)气管内滴入双重打击致急性肺损伤(acute lung injury,ALI)的炎症机制、激素干预效果的差异及潜在机制.方法 健康雄性SD大鼠48只,随机分为6组(每组8只):生理盐水(NS)组、LPS组、LPS-HCl组、NS+地塞米松(Dex)组、LPS+Dex组和LPS-HCl+Dex组.检测各组支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中细胞总数、蛋白含量,肺湿/干重比(W/D),肺组织病理评分,血清和BALF中TNF-α、IL-1β、IL-4、IL-10的含量及肺组织中糖皮质激素受体(GR)mRNA水平.结果 ①LPS-HCl组BALF中蛋白含量高于LPS组(P＜0.05),LPS+Dex组BALF中细胞总数、蛋白含量以及肺W/D均低于LPS组(P值均＜0.05),而LPS-HCl+Dex组只有肺W/D比LPS-HCl组降低(P＜0.05);②LPS+Dex组和LPS-HCl+Dex组的病理评分均较激素干预之前显著降低(P值均＜0.01),且LPS-HCl+Dex组评分明显高于LPS+Dex组(P＜0.01);③LPS-HCl组BALF中IL-1β、IL-4水平明显高于LPS组(P值均＜0.05),LPS+Dex组和LPS-HCl+Dex组血清和BALF中TNF-α的含量较激素干预之前降低(P值均＜0.01),IL-10的含量升高(P值均＜0.05),同时LPS+Dex组BALF中IL-1β的含量下降(P＜0.05);④LPS+Dex组和LPS-HCl+Dex组肺组织中GR mRNA水平均较激素干预之前升高(P值均＜0.05),而NS+Dex组肺组织中GR mRNA水平较NS组显著降低(P＜0.01).结论 一次打击及双重打击所致ALI/急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)在蛋白渗漏、细胞因子水平方面存在一定差异,说明ALI/ARDS的炎症反应与致病因素是紧密相连的;LPS组的激素干预效果优于LPS-HCl组,这可能与两种模型的GR表达水平、功能状态及病理损伤特点不同有关.

Cytokines,glucocorticoid receptor mRNA and discrepancy of efficacy of steroid in rat acute lung injury models induced by two different risk factors

Objective To explore the inflammatory mechanism,curative efficacy of glucocorticoids in acute lung injury(AM) models induced by lipopolysaccharide(LPS) one hit and LPS-hydrochloric acid(HCl) two hit and potential mechanism. Methods Forty-eight male SD rats were divided randomly into six groups:NS group,LPS group,LPS-HCl group,NS+Dex group,LPS+Dex group, LPS-HCl+Dex group. The total leukocytes and protein content in BALF, W/D, the histological grade, the level of GRmRNA and the concentrations of TNF-α, IL-1β, IL-4 and IL-10 in serum and BALF in every group were measured. Results In LPS+Dex group,the total leukocytes, protein concentration in BALF and W/D were lower than those in LPS group(all P＜0.05). Compared with LPS-HCl group,only W/D in LPS-HCl+Dex group was decreased the corresponding model groups(all P＜0.01 ). Compared with LPS+Dex group, the grade of LPS-HCl+undetected. In LPS-HCl group, the concentration of IL-1β, IL-4 in BALF were higher than those of LPS group (all P＜0.05 ). In LPS + Dex and LPS- HCl+Dex groups, the concentration of TNF- α in BALF and serum was decreased(all P＜0.01) and the concentration of IL-10 in BALF and serum was increased(all P＜0.05). In LPS +Dex group,the concentration of IL-1β in BALF was lower than that in LPS group( P＜corresponding model groups(all P＜0.05), while the parameter in NS+Dex group was lower than that in NS group( P＜0.01). Conclusions The content of cytokines and the permeability in one hit and two hit ALI/ARDS models are not consistent. It suggests that inflammation mechanism of ALI/ARDS is related to different risk factors. GCs can alleviate the pulmonary injury in two model groups, but the efficacy on LPS group is better than LPS-HCl group. It may be related to the number and function situation of GR and the differences in pathogenesis of two model groups.