右美托咪定后处理对内毒素致大鼠急性肺损伤的影响

Effect of dexmedetomidine postconditioning on acute lung injury induced by lipopolysaccharide in rats

目的 探讨右美托咪定后处理对内毒素（LPS）致大鼠急性肺损伤（ALI）的影响.方法 雄性SD大鼠50只,体重200～250 g,7～8周龄,采用随机数字表法,将其分为5组（n=10）：对照组（C组）、LPS组和不同剂量右美托咪定后处理组（LD组、MD组和HD组）.LPS组、LD组、MD组和HD组尾静脉注射LPS 8 mg/kg制备大鼠ALI模型.注射LPS1h时,LD组、MD组和HD组分别腹腔注射右美托咪定5、10和15 μg/kg,C组和LPS组腹腔注射等容量生理盐水.给予右美托咪定后6h时,左心取血后处死大鼠,收集支气管肺泡灌洗液（BALF）,用ELISA法测定血浆和BALF中TNF-α和IL-6的浓度;取肺组织,测定湿重/干重（W/D）比值,光镜下行肺组织病理学损伤评分,用RT-PCR法测定Toll样受体4（TLR4） mRNA表达.结果 与C组比较,LPS组、LD组、MD组及HD组肺组织W/D比值、病理学损伤评分、血浆和BALF中TNF-α和IL-6的浓度升高,肺组织TLR4 mRNA表达上调（P＜0.05）.与LPS组和LD组比较,MD组和HD组肺组织W/D比值、病理学损伤评分、血浆和BALF中TNF-α和IL-6的浓度降低,肺组织TLR4 mRNA表达下调（P＜0.05）.LPS组与LD组组间、MD组与HD组组间上述指标比较差异无统计学意义（P＜0.05）.结论 右美托咪定后处理可减轻LPS致大鼠ALI,其机制可能与抑制TLR4 mRNA表达上调,从而减轻炎性反应有关.

Objective To investigate the effect of dexmedetomidine postconditioning on acute lung injury （ALI） induced by lipopolysaccharide （LPS） in rats.Methods Fifty male Spragne-Dawley rats,aged 7-8 weeks,weighing 200-250 g,were randomly divided into 5 groups （n =10 each） using a random number table：control group （group C）,LPS group and postconditioning with 3 different doses of dexmedetomidine groups （LD,MD and HD groups）.ALI was induced with LPS 8 mg/kg injected via the caudal vein in LPS,LD,MD and HD groups.Dexmedetomidine 5,10 and 15 μg/kg were injected intraperitoneally in LD,MD and HD groups,respectively,at 1 h after LPS injection.The equal volume of normal saline was injected intraperitoneally in C and L groups.Blood samples were taken from the left ventricle at 6 h after dexmedetomidine administration,then the animals were sacrificed and broncheoalveolar lavage fluid （BALF） was collected.The concentrations of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in plasma and BALF were detected by ELISA.The lungs were removed for microscopic examination of pathological changes and for determination of wet/dry lung weight （W/D） ratio and expression of Toll-like receptor 4 （TLR4） mRNA （by RT-PCR） in lung tissues.Results Compared with group C,W/D ratio,pathological scores,and the concentrations of IL-6 and TNF-α in plasma and BALF were significantly increased,and the expression of TLR4 mRNA was up-regulated in LPS,LD,MD and HD groups.Compared with LPS and LD groups,W/D ratio,pathological scores,and the concentrations of IL-6 and TNF-α in plasma and BALF were significantly decreased,and the expression of TLR4 mRNA was down-regulated in MD and HD groups.There was no significant difference in the parameters mentioned above between LPS and LD groups,and between MD and HD groups.Conclusion Dexmedetomidine postconditioning can alleviate ALI induced by LPS in rats,and up-regulated TLR4 mRNA expression and reduced inflammatory responses may be involved in the mechanism.