ghrelin对脓毒血症大鼠肺脏炎症及核苷酸结合寡聚域2和受体相互作用蛋白2 mRNA表达的影响  

Effects of ghrelin on inflammation and nucleotide-binding oligomerzation domain 2/ receptor interacting protein 2 in the lung of septic rats

作　　者：彭志友[1] 封小美[1] 薛庆生[1] 于布为[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院麻醉科,200025

出　　处：《上海医学》2011年第8期586-589,565,共4页Shanghai Medical Journal

基　　金：国家自然科学基金资助项目(30901409)

摘　　要：目的研究ghrelin对脓毒血症大鼠肺脏中性粒细胞浸润、炎性细胞因子[肿瘤坏死因子(TNF)-α和白细胞介素(IL)-6]及核苷酸结合寡聚域2(NOD2)和受体相互作用蛋白2(RIP2)mRNA表达的影响。方法 24只雄性Sprague-Dawley(SD)大鼠随机分为4组:假手术组(Sham组)、假手术+ghrelin组(Sham+ghrelin组)、脓毒血症组(CLP组)和脓毒血症+ghrelin组(CLP+ghrelin组)。采用盲肠结扎穿孔(CLP)的方法建立脓毒血症大鼠模型。Sham+ghrelin组和CLP+ghrelin组分别于假手术或CLP后即刻经尾静脉注射10 nmol/kgghrelin,Sham组和CLP组于相应时间点尾静脉注射等量0.9%氯化钠溶液,给药速率为0.2 mL/min。于假手术或CLP后6 h麻醉下处死大鼠,取肺组织,光学显微镜下观察肺组织病理学变化,并测定髓过氧化物酶(MPO)活性、TNF-α和IL-6水平以及NOD2和RIP2 mRNA的表达。结果与Sham组和Sham+ghrelin组比较,CLP组和CLP+ghrelin组肺组织MPO活性、TNF-α和IL-6水平、NOD2和RIP2 mRNA的表达均显著升高(P值均<0.05);CLP+ghrelin组肺组织MPO活性、TNFα-和IL-6水平、NOD2和RIP2 mRNA的表达均显著低于CLP组(P值均<0.05)。结论 ghrelin可改善脓毒血症大鼠肺脏中性粒细胞的浸润、下调肺组织炎性细胞因子(TNF-α和IL-6)的表达,其作用可能与抑制NOD2/RIP2信号通路有关。Objective To investigate the effect of ghrelin on neutrophil infiltration,expression of inflammation factors（tumor necrosis factors-α and interlukin-6）,nucleotide-binding oligomerzation domain 2（NOD2） and receptor interacting protein 2（RIP2） in a rat model of sepsis.Methods Twenty-four male SD rats were randomly divided into four groups,namely,a sham group： abdomen was opened and closed followed by infusion of normal saline;sham＋ghrelin group： sham operation plus infusion of ghrelin;CLP group： sepsis was induced by cecal ligation and puncture（CLP） followed by infusion of normal saline;and CLP＋ghrelin group： CLP was followed by infusion of ghrelin.Ghrelin（10 nmol/kg） was given via the tail vein at the rate of 0.2 mL/min and the same volume of normal saline was infused as control.Animals were killed under anesthesia and the lungs were harvested at 6 h after CLP or sham operation for examination of histopathology,myeloperoxidase（MPO） activity,inflammatory cytokines,and mRNA levels of NOD2 and RIP2.Results Compared with sham group and sham＋ghrelin group,MPO activity,TNF-α and IL-6,and NOD2 and RIP2 mRNA levels in the lung were significantly increased in CLP group and CLP＋ghrelin group after CLP（all P0.05）.Compared with CLP group,MPO activity,TNF-α and IL-6,and NOD2 and RIP2 mRNA levels in the lung were significantly increased in CLP＋ghrelin group（all P0.05）.Conclusion Ghrelin can improve the neutrophil infiltration,decrease inflammatory cytokine（TNF-α,IL-6） expression in septic rats,which might be related to the inhibition of NOD2/RIP2 pathway.

关 键 词：GHRELIN 脓毒血症 核苷酸结合寡聚域2 受体相互作用蛋白2 细胞因子 

分 类 号：R459.7[医药卫生—急诊医学]