脓毒症大鼠多器官内信号转导和转录激活因子3变化及其作用  被引量:17

Activation of signal transducer and activator of transcription 3 in multiple organs of rats with sepsis

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作  者:翟秀珍[1] 姚咏明 王松柏 董宁 于燕 盛志勇 

机构地区:[1]解放军第三○四医院全军烧伤研究所基础部

出  处:《中华创伤杂志》2004年第3期146-149,共4页Chinese Journal of Trauma

基  金:国家重点基础研究发展规划资助项目 (G1 9990 542 0 3);国家杰出青年基金资助项目 ( 30 1 2 50 2 0 );北京市"十五"科技计划重大资助项目 (H0 2 0 92 0 0 2 0 530 )

摘  要:目的 观察盲肠结扎穿孔 (CLP)所致脓毒症大鼠主要组织中信号转导和转录激活因子 3 (STAT3 )的活化规律 ,并探讨STAT3抑制剂对多器官功能损害的影响。 方法 采用CLP模型 ,大鼠随机分为正常对照组 (10只 )、假手术组 (10只 )、CLP组 (40只 )、STAT3抑制剂———雷帕霉素干预组 (2 4只 )。留取肝、肺、肾、肠组织测定STAT3的DNA结合活性和mRNA表达水平 ,同时测定血清丙氨酸氨基转移酶 (ALT)和肌酐 (Cr)含量及肺组织髓过氧化物酶 (MPO)和肠组织二胺氧化酶 (DAO)活性。 结果 CLP早期肝、肺组织中STAT3即迅速活化 ,2 4h达峰值 ;而在肾、肠组织中未检测到STAT3的活化。同时 ,肝、肺组织STAT3mRNA表达显著增强 ,而肾、肠其表达仅略有升高。雷帕霉素干预肝、肺组织STAT3活性显著性下降 (P <0 .0 5或 0 .0 1) ;并且血清ALT水平和MPO活性在CLP后 2 4及 48h显著下降 (P <0 .0 5或 0 .0 1) ,Cr水平在 2 4h也有不同程度的改善 (P<0 .0 5)。但雷帕霉素干预对肠组织DAO活性无明显影响 (P >0 .0 5)。 结论 在脓毒症时 ,STAT3可能是介导组织损害的重要信号途径之一 ,抑制STAT3的活化有助于减轻肝、肺。Objective To investigate the activation law of signal tr ansducer and activator of transcription 3 (STAT3) in vital organs of rats with s epsis induced by cecal ligation and puncture (CLP) and discuss the potential eff ect of STAT3 inhibitor on multiple organ dysfunction. Methods A sepsis model induced by cecal ligation and puncture (CLP) was used and 84 m ale Wistar rats randomly divided into normal control group (n=10), sham operatio n group (n=10), CLP group (n=40), and rapamycin (RPM, STAT3 specific inhibitor) pretreatment group (n=24). At serial time points, animals in each group were sac rificed. Then, the liver, the lungs, the kidneys and the small intestine samples were harvested for detection of DNA-binding activity and mRNA expression of ST AT3. Meanwhile, activities of pulmonary myeloperoxidase (MPO) and intestinal dia mine oxidase (DAO) as well as serum ALT and BUN contents were also determined. Results STAT3 activities rapidly increased in the liver and the lungs at the early stage of CLP and peaked at the 24th hour. While no activ ities of STAT3 were found in the small intestine and the kidneys. In the meantim e, the STAT3 mRNA expression was markedly up-regulated in the liver and the lun gs following CLP while slightly increased in the small intestine and the kidneys . Pretreatment with RPM significantly decreased STAT3 activities in the liver an d the lungs ( P < 0.05 or 0.01) . In comparison with the CLP group, RPM treatment could markedly reduce serum ALT as well as Cr levels and pulmonary MPO activities 24-48 hours after CLP respectively ( P <0.05 or 0.01 ), excep t for intestinal DAO activity ( P >0.05). Conclusions STA T3 may be one of signal transduction pathways mediating tissue injury when CLP s epsis is induced in rats. Inhibition of STAT3 activation can help attenuate the development of multiple organ dysfunction.

关 键 词:信号传递 脓毒症 多器官功能衰竭 转录激活因子3 动物模型 

分 类 号:R631[医药卫生—外科学]

 

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