二硫代氨基吡咯烷预先给药对内毒素诱发大鼠急性肺损伤的影响

目的 评价二硫代氨基吡咯烷预先给药对LPS诱发大鼠急性肺损伤的影响.方法 健康成年Wistar大鼠54只,雌雄各半,体重180～220 g,随机分为3组:对照组(C组,n=6)、LPS组(n=24)和二硫代氨基毗咯烷预先给药组(PDTC组,n=24).LPS组腹腔注射LPS 8 mg/kg;PDTC组经尾静脉注射二硫代氨基吡咯烷120 mg/kg,30 min后腹腔注射LPS 8 mg/kg;C组注射等容量生理盐水.LPS 组和PDTC组分别于给予LPS后1、3、6和12 h时,C组于给予生理盐水后即刻,经下腔静脉取血后,各处死6只大鼠,取肺组织,采用双抗体夹心ABC-ELISA法测定血清IL-6浓度,计算肺组织湿重与干重的比值(W/D比),采用免疫组化法测定肺组织HSP70的表达和NF-κB 的活性,电镜下观察肺组织超微结构.结果 与C组比较,LPS组和PDTC组肺组织W/D比和NF-κB活性升高,HSPT0表达上调,血清IL6浓度升高(P<0.01);与LPS组比较,PDTC组肺组织W/D比和NF-κB活性降低,HSP70表达上调,血清IL-6浓度降低(P<0.01),肺组织病理损伤减轻.结论 二硫代氨基吡咯烷预先给药可减轻LPS诱发大鼠急性肺损伤,其机制可能与抑制肺组织NF-κB的活性和上调HSPT0的表达有关.

Protective effect of pyrrolidine dithiocarbamate pretreatment on lung against LPS-induced injury in rats

Objective To investigate the protective effect of pyrrolidine dithiocarbamate (PDTC) pretreatment on lung agaillst LPS-indueed injury in rats.Methods Fifty-four Wistar rats of both sexes weighing 180-220 g were randomly idivided into 3 groups:group I normal control(group C,n=6);group Ⅱ LPS (group L,n=24)and group Ⅲ PDTC(group P,n=24).Endotoxemia was induced by intraperitoneal LPS 8 mg/kg in group Ⅱ and Ⅲ.In group Ⅲ PDTC 120 mg/kg was injected iv at 30 min before IP LPS.Venous blood samples were collected at 1,3,6 and 12 h after LPS administration in group L and P and after normal saline administration in group C for determination of serum IL-6 concentration by ELISA.Six animals were killed at each time point after blood sample collection.The lungs were removed for microscopic examination and determination of W/D lung weight ratio,HSP70 expression and NF-κB activity.Results Intraperitoneal LPS significantly increased serum IL-6 concentration and W/D lung weight ratio,HSP70 expression and NF-κB activity in group Ⅱ.PDTC pretreatment significantly attenuated LPS-induced increase in serum IL-6 concentration,W/D lung weight ratio andNF-κB activity.The lung histologic dalnage induced by LPS Wag also ameliorated by pretreatment with PDTC.Conclusion Pyrrolidine dithiocarbamate pretreatment Can protect lung against LPS-induced injury through inhibition of activation of lung tissue NF-κB and up-regulation of expression of HSP70.