15d-PGJ2对大鼠内毒素性急性肺损伤的影响

Effect of 15d-PGJ2 on endotoxin-induced acute lung injury in rats

目的 评价15-脱氧-△12,14-前列腺素J2（15d-PGJ2）对大鼠内毒素性急性肺损伤的影响.方法 健康雄性SD大鼠40只,3～5月龄,体重220～ 250 g,采用随机数字表法分为4组（n=10）：对照组（C组）、15d-PGJ2组、LPS组和LPS＋ 15d-PGJ2组.C组和15d-PGJ2组分别尾静脉注射等容量生理盐水和15d-PGJ2 0.3 mg/kg;LPS组和LPS＋ 15d-PGJ2组尾静脉注射LPS 6 mg/kg制备急性肺损伤模型,然后分别尾静脉注射等容量生理盐水和15d-PGJ2 0.3 mg/kg.注射LPS后4h时,腹主动脉取血样行血气分析,记录PaO2,然后处死大鼠,取肺组织,光镜下观察病理学结果,测定湿重/干重比值（W/D比值）,采用ELISA法测定TNF-α、IL-8和中性粒细胞趋化因子-1（CINC-1）的含量,采用Western blot法检测NF-κB p65和IκB-α的表达水平.结果 与C组比较,15d-PGJ2组PaO2、肺组织W/D比值、TNF-α、IL-8、CINC-1的含量和NF-κB p65、IκB-α的表达差异无统计学意义（P＞0.05）,LPS组和LPS＋ 15d-PGJ2组PaO2降低,肺组织W/D比值、TNF-α、IL-8、CINC-1的含量升高,NF-κB p65表达上调,IκB-cα表达下调（P＜0.05）;与LPS组比较,LPS＋ 15d-PGJ2组PaO2升高,肺组织W/D比值、TNF-α、IL-8、CINC-1的含量降低,NF-κB p65表达下调,IκB-α表达上调（P＜0.05）,病理学损伤减轻.结论 15d-PGJ2可减轻大鼠内毒素性急性肺损伤.

Objective To evaluate the effect of 15-deoxy-△12,14-prostaglandin J2 （15d-PGJ2） on endotoxin-induced acute lung injury （ALI） in rats.Methods Forty healthy male Sprague-Dawley rats, aged 3-5 months, weighing 220-250 g, were randomly divided into 4 groups （n =10 each） using a random number table： control group （group C）, 15d-PGJ2 group, lipopolysaccharide （LPS） group, and LPS ＋15d-PGJ2 group.In group 15d-PGJ2, 15d-PGJ20.3 mg/kg was injected via the tail vein, while the equal volume of normal saline was given in group C.In LPS and LPS＋15d-PGJ2 groups, ALI was produced with LPS 6 mg/kg injected through the tail vein, and then the equal volume of normal saline and 15d-PGJ2 0.3 mg/kg were injected, respectively.At 4 h after LPS injection, blood samples were drawn from the abdominal aorta for blood gas analysis, and arterial oxygen partial pressure （PaO2） was recorded.The rats were then sacrificed, lungs were removed for microscopic examination, and for determination of wet/dry lung weight ratio （W/D ratio）, TNF-α, IL-8 and cytokine-induced neutrophil chemoattractant-1 （CINC-1） contents （by enzyme-linked immunosorbent assay） , and nuclear factor kappa B （NF-κB） p65 and IκB-α expression （by Western blot）.Results Compared with group C, no significant change was found in PaO2, W/D ratio, contents of TNF-α, IL-8 and CINC-1, and expression of NF-κB p65 and IκB-α in group 15d-PGJ2 （P〉0.05）, and PaO2 was significantly decreased, W/D ratio and contents of TNF-α,IL-8 and CINC-1 were increased, the expression of NF-κB p65 was up-regulated, and the expression of IκB-α was down-regulated in LPS and LPS＋ 15d-PGJ2 groups （P〈0.05）.Compared with group LPS,PaO2 was significantly increased, W/D ratio and contents of TNF-α, IL-8 and CINC-1 were decreased, the expression of NF-κB p65 was down-regulated, and the expression of IκB-α was up-regulated （P〈0.05）,and the pathological changes were attenuated in group LPS＋ 15d-PGJ2.Conclusion 15d-PGJ2 can mitigate endotoxin-induced ALI in rats.