外源性一氧化碳释放分子对脓毒症大鼠肺组织高迁移率族蛋白B1表达的影响

目的 研究外源性一氧化碳释放分子（CORM-2）对脓毒症大鼠肺组织高迁移率族蛋白B1（HMGB1）表达的影响.方法 盲肠结扎穿孔（CLP）法制备脓毒症动物模型,150只雄性Wistar大鼠,随机分为对照组（C组）、脓毒症模型组（CLP组）和CORM-2组（n=50）,分别于术后6、12、24、48、72 h处死,采用酶联免疫吸附法（ELISA）检测肺组织匀浆中HMGB1表达水平,实时荧光定量聚合酶链反应（real-time PCR）法检测肺组织匀浆中HMGB1 mRNA的表达水平;凝胶阻滞电泳分析技术（EMSA）检测肺组织STAT3的DNA结合活性;同时检测肺组织丙二醛（MDA）含量和湿/干重比（W/D）;流式细胞仪测定细胞凋亡率.结果 与C组比较,CLP、CORM-2组大鼠肺组织HMGB1 mRNA及蛋白表达水平升高,STAT3的DNA结合活性表达升高,肺组织匀浆中MDA含量显著升高,细胞凋亡率和W/D升高;与CLP组比较,CORM-2组大鼠肺组织HMGB1 mRNA及蛋白表达水平下降,STAT3的DNA结合活性表达降低,肺组织匀浆中MDA含量显著下降,细胞凋亡率和W/D降低.结论 CORM-2能够下调肺组织HMGB1表达,减轻脓毒症性肺损伤.

Effect of extrinsic carbon monoxide releasing-molecule-2 on the expression of high mobility group box 1 in rats with sepsis-induced lung injury

Objective To investigate the effect of extrinsic carbon monoxide releasing-molecule-2 （CORM-2） on the expression of high mobility group box 1 （HMGB1） in rats with sepsis-induced lung injury.Methods The animal model of sepsis was established by ceal ligation and puncture （CLP） in 150 Wistar male rats,which were randomly divided into 3 groups：C group,CLP group and CORM-2 group.At 6,12,24,48,72 h,HMGB1 concentration in lung homogenate was detected by ELISA.Lung HMGB1 mRNA was detected with real-time fluorescent quantitative polymerase chain reaction （real-time RT-PCR）,DNA-binding activity of STAT3 was analyzed by electrophoretic mobility shift assay （EMSA）.Malonaldehyde （MDA） content in lung tissue and the wet-to-dry （W/D） weight ratio of lung tissue were determined.The extent of cell apoptosis was determined by flow cytometry.Results Compared with C group,gene and protein expression of HMGB1 in groups CLP,CORM-2 were increased,DNA-binding activity of STAT3 and MDA content in lung homogenate were raise,as well as the rates of apoptosis and lung W/D weight ratio.Compared with CLP group,gene and protein expression of HMGB1 in group CORM-2 was decreased,DNA-binding activity of STAT3 and MDA content in lung homogenate were lower,as well as the rates of apoptosis and lung W/D weight ratio.Conclusions CORM-2 intervention may down-regnlate HMGB 1 expression and attenuate lung injury in CLP-induced septic rats.