己酮可可碱对内毒素肺损伤大鼠炎性细胞因子变化的干预作用  

Interventional effect of pentoxifylline on the changes of inflammatory cytokine genes in lipopolysaccharide-induced acute lung injury in rats

作　　者：徐剑铖[1] 毛宝龄[1] 钱桂生[1] 冯英凯[1] 田玉恒[1] 

机构地区：[1]第三军医大学新桥医院全军呼吸内科研究所

出　　处：《第三军医大学学报》2004年第10期845-847,共3页Journal of Third Military Medical University

基　　金：国家自然科学基金资助项目 ( 3950 0 0 6 4) ;重庆市科技计划资助项目 ( 1997 6 )~~

摘　　要：目的　观察内毒素性肺损伤大鼠肺组织及外周血炎性细胞因子的变化 ,探讨己酮可可碱 (pentoxifylline ,PTX)的干预作用。方法　 72只雄性Wistar大鼠分为 :①内毒素 1h组 (n =6) ,②内毒素 2h组 (n =6) ,③内毒素 4h组 (n =6) ,④内毒素 6h组 (n =12 ) ,⑤生理盐水对照组 (n =12 ) ,⑥PTX 1h组 (n =6) ,⑦PTX 2h组 (n =6) ,⑧PTX 4h组 (n =6) ,⑨PTX 6h组(n =12 )。采用静脉注射LPS的方法复制内毒素性肺损伤模型 ,PTX组致伤后立即静脉注射PTX 2 0mg/kg ,并以 6mg·kg-1 ·h-1 维持。各组动物于设定的时相点放血活杀 ,用ELISA法或胸腺细胞增殖法测定血清TNF α、IL 6、IL 8含量及IL 1活性 ;斑点杂交检测肺组织中TNF α、IL 1β、IL 6、IL 8mRNA表达。 结果　①内毒素致伤后各组肺组织内TNF α、IL 1β、IL 6、IL 8mRNA的表达强度 ,均非常显著高于生理盐水对照组 (P <0 0 1)。PTX治疗后 ,内毒素致伤大鼠肺组织内TNF α、IL 1β、IL 6、IL 8mRNA的相对含量较未接受PTX治疗大鼠有一定程度的减少。②内毒素致伤后各组血清中TNF α、IL 1、IL 6、IL 8含量或活性均非常明显高于生理盐水对照组 (P <0 0 1)。PTX 6h组血清中TNF α、IL 1、IL 6、IL 8含量或活性 ,明显低于内毒素 6h组(P <0 .0 1)。结论　内毒素肺?Objective To investigate the interventional effect of pentoxifylline (PTX) on the expressions of TNF α, IL 1β, IL 6, and IL 8 mRNA in the lung and the levels of TNF α, IL 1, IL 6, and IL 8 in serum in rats with lipopolysaccharide induced acute lung injury (ALI). Methods A total of 72 Wistar rats were divided into 9 groups randomly: (LPS) 1 h group ( n =6), 2 h group ( n =6), 4 h group ( n =6), 6 h group ( n =12); and normal saline control group ( n =12), and PTX 1 h group ( n =6), 2 h group ( n =6), 4 h group ( n =6), 6 h group ( n =12). The expressions of TNF α, IL 1β, IL 6, and IL 8 mRNA were detected by Dot Blotting. The levels of TNF α, IL 1β, IL 6, and IL 8 were determined by ELISA. Results Compared with those in the normal saline control group, the expression levels of TNF α, IL 1β, IL 6, and IL 8 mRNA in the injured lungs increased significantly ( P <0.01), and the levels of these cytokines in serum increased in LPS treated groups ( P <0.01). The expressions of TNF α, IL 1β, IL 6, and IL 8 mRNA were inhibited markedly in PTX treated groups. The levels of these cytokines in serum were lower in PTX groups than those in LPS treated groups ( P <0.01). Conclusion Increased expression levels of TNF α, IL 1β, IL 6, and IL 8 mRNA are found in rat lungs with lipopolysaccharide induced ALI. The levels of these cytokines in serum also increase significantly. TNF α, IL 1β, IL 6, and IL 8 may contribute to lipopolysaccharide induced ALI, since these cytokines are highly expressed at both the mRNA and the protein levels. PTX can inhibit the production of these inflammatory cytokines in vivo and the mRNA expression in the lung tissues.

关 键 词：急性肺损伤 炎症细胞因子 内毒素 己酮可可碱 

分 类 号：R392.11[医药卫生—免疫学] R563[医药卫生—基础医学]