基础医学与临床 ›› 2007, Vol. 27 ›› Issue (4): 440-444.

• 研究论文 • 上一篇    下一篇

信号转导和转录激活子-1与脓毒症大鼠肺炎病反应的关系

翟秀珍 王松柏 刘俊堂 柴军英 李艳红   

  1. 北方学院第一附属医院神经内科 解放军251医院麻醉科 解放军251医院麻醉科 解放军251医院麻醉科 解放军251医院麻醉科
  • 收稿日期:2006-02-20 修回日期:2006-09-21 出版日期:2007-04-25 发布日期:2007-04-25
  • 通讯作者: 王松柏

Effect of singal transducer and activator of transcription -1 on pulmonary inflammatory response in septiv rats

  

  • Received:2006-02-20 Revised:2006-09-21 Online:2007-04-25 Published:2007-04-25

摘要: 目的 探讨信号转导子和转录激活子-1(signal transducer and activator of transcription,STAT-1)活化与脓毒症大鼠肺组织炎症反应的关系及白介素(IL)-6、-10在其中的作用。方法 用盲肠结扎穿孔术(CLP)复制大鼠腹腔感染,随机分为若干组。用RT-PCR和ELISA法测定血浆和肺IL-6 、IL-10mRNA和蛋白水平;凝胶电泳阻滞分析(EMSA)测定STAT-1的DNA结合活性;比色法测定肺髓过氧化酶(MPO)活性、病理组织学观察炎症反应程度。结果 与正常大鼠相比, CLP后各时间点肺STAT活性、血浆和肺MPO、病理学评分、IL-6 、IL-10mRNA及蛋白含量均明显升高。雷帕霉素(RPM)处理后,上述指标均显著回降;而IL-10 mRNA表达和蛋白含量显著升高。结论 抑制STAT-1 活化可缓解脓毒症所致肺组织损伤;这一作用可能与RPM通过抑制STAT的激活而调节IL-10及其他炎症介质表达相关。

Abstract: Objective The purposes of the present study were to assess ①the effect of signal transducer and activator of transcription (STAT) on pulmonary injury induced by cecal ligation puncture (CLP) in septic rats; ②the significance of interleukin (IL)-6 and IL-10 expression in pulmonary injury mediated by STAT in septic rats. Methods Sepsis of rats was induced by CLP. 56 male Wistar rats were randomly divided into normal control (n=8), CLP group (n=24), and inhibitor (rapamycin, RPM) of STAT pretreatment group (n=24). At serial time points in each group, animals were sacrificed. Then, pulmonary tissue and serum samples were harvested to determine IL-6 and IL-10 mRNA expression levels by reverse transcription polymerase chain reaction (RT-PCR) and protein expression levels by enzyme-linked immunosorbent assay (ELISA). Meanwhile, pulmonary STAT1 DNA-binding activity was detected by electrophoretic mobility shift assay (EMSA) and activity of myeloperoxidase (MPO) as well as histopathology were also evaluated. Results Compared to normal control, pulmonary STAT1 activity at 6h, 24h and 48h following CLP significantly elevated (P<0.01). In the meantime, pulmonary MPO, histopathologic scoring as well as IL-6 and IL-10 mRNA and protein expression levels in lung or serum markedly increased respectively. Following pretreatment with RPM, pulmonary STAT1 activity, MPO and histopathologic scoring decreased compared to CLP group, IL-10 expression significantly elevated, IL-6 levels without alteration at the same time. Conclusion These data suggest that severe intra-abdoment infection elevates pulmonary STAT1 activity and induces injury of remote lung, and inhibiting the activation of STAT1 attenuates pulmonary tissue damage, however contributions from STAT1 driven expression of IL-10 as well as IL-6 may be needed in a balanced fashion to maximize the animals' ability to survive septic challenge.