持续输注脂肪乳对大鼠内毒素诱导急性肺损伤的影响及机制

Effect of continuous infusion of lipid emulsions on endotoxin induced acute lung injury and mechanism in rats

目的比较3种脂肪乳剂对脂多糖(LPS)诱导的急性肺损伤大鼠(ALI)IL-1β表达及肺泡上皮细胞凋亡的影响。方法 100只SD幼年大鼠按随机数字分为Blank组(生理盐水+生理盐水)、LPS组(生理盐水+LPS)、Intra组(20%脂肪乳Intralipid+LPS)、Clino组(20%脂肪乳Clinoleic+LPS)和Omega组(10%脂肪乳Omegaven+LPS)。各组分别采用生理盐水或脂肪乳剂处理7 d;并均在取标本前8 h于气管内滴入生理盐水或脂多糖,建立ALI大鼠模型;观察各组大鼠肺组织的病理改变,检测肺泡上皮细胞凋亡,并计算凋亡指数(AI),测定IL-1βmRNA变化及蛋白浓度。结果与Intra组相比,Clino组和Omega组IL-1βmRNA表达及IL-1β水平较低(P均<0.005),而Clino组和Omega组IL-1βmRNA浓度及蛋白水平差异无统计学意义(P>0.005)。各组大鼠肺组织均可见明显炎症细胞浸润和出血。Clino组和Omega组凋亡系数(AI)均低于LPS组和Intra组(P均<0.005);Clino组和Omega组AI值差异无统计学意义(P>0.005)。结论 Clinoleic和Omegaven可能通过降低IL-1β而减轻ALI大鼠炎症反应,并减少肺泡上皮细胞凋亡。

Objectives To compare the effects of three kinds of lipid emulsions on IL-1β expression and alveolar epi-thelial cell apoptosis in LPS-induced acute lung injury （ALI） in rat. Methods One hundred young Sprague-Dawley rats were divided into control group, LPS group, Intra group （20% Intralipid）, Clino group （20% Clinoleic） and Omega group （10% Omegaven）. Each group was treated with normal saline or different lipid emulsions for seven days. The rats were intratra- cheally instilled with normal saline or LPS to establish the rat model of ALI 8 hours before sacrifice. The pathologic chan- ges in lung tissue section were observed and the apoptosis index （AI） was measured. The expression level of IL-1β mRNA was determined by RT-PCR. Meanwhile the concentration of IL-1β in broncho-alveolar lavage fluid （BALF） was measured by enzyme-linked immunospecific assay （ELISA）. Results The expression of IL-1β mRNA and the level of IL-1β in BALF in Intra group were significantly elevated as compared to Clino group and Omega group （both P〈0.005）, but there was no significant difference （P〉0.005） between Clino group and Omega group. HE-stained lung tissues showed obvious infiltra-tion of inflammatory cells and bleeding in all groups. The AI was lower in Clino group and Omega group than in LPS group and Intra group （both P〈0.005） and the difference was not significant between Clino group and Omega group （P〉0.005）. Conclusions Clinoleic and Omegaven may relieve inflammation by down-regulating IL-1β and reduce the alveolar epithe-lial cell apoptosis in rats with acute lung injury.