摘要
目的 探讨Janus激酶 (JAK ) /信号转导和转录激活因子 (STAT)通路对脓毒症大鼠肺组织高迁移率族蛋白B1(HMGB1)mRNA表达的调节作用及其意义。方法 采用大鼠盲肠结扎穿孔 (CLP)模型造成脓毒症 ,98只动物随机分为正常对照组、脓毒症组、JAK2抑制剂AG490处理组和STAT抑制剂雷帕霉素 (RPM )处理组。采用逆转录 聚合酶链反应 (RT PCR)测定肺组织HMGB1mRNA表达水平 ,同时测定髓过氧化物酶 (MPO )活性。结果 与正常对照组相比(0 .2 0 7± 0 .0 19) ,CLP组 2、6、2 4h肺组织HMGB1mRNA均显著升高 (P <0 .0 5～ 0 .0 1) ,分别为0 .471± 0 .0 3 5、0 .3 69± 0 .0 2 8、0 .491± 0 .0 42。AG490处理组 2h肺组织HMGB1mRNA表达明显抑制 (P <0 .0 5 ) ,RPM处理组 2、6、2 4、48hHMGB1均显著下降 (P <0 .0 5～ 0 .0 1)。同时 ,AG490、RPM处理组 2 4、48h肺组织MPO活性显著降低 (P <0 .0 5～ 0 .0 1)。结论 JAK/STAT信号通路参与了脓毒症肺组织HMGB1mRNA表达的病理过程 ,抑制其活化有助于下调HMGB1mRNA表达并减轻肺损伤。
Objective To investigate the effect of Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway on mediating pulmonary mRNA expression of high mobility group box-1 protein (HMGB1) in rats with sepsis.Methods Using a sepsis model induced by cecal ligation and puncture (CLP),98 male Wistar rats were randomly divided into normal control group ( n =10),CLP group ( n =40),AG490 treatment group (JAK2 inhibitor,n =24),and rapamycin (RPM) treatment group (STATs inhibitor,n =24).At the scheduled time points animals in each group were sacrificed,then lung tissue samples were harvested to determine HMGB1 mRNA expression and myeloperoxidase (MPO) activity.Results Compared to normal controls (0.207±0.019),pulmonary HMGB1 mRNA levels were significantly increased at 2,6 and 24h after CLP ( P <0.05 or 0.01),being 0.471±0.035,0.369±0.028,and 0.491±0.042,respectively.Treatment with AG490 could markedly inhibit pulmonary HMGB1 mRNA levels at 2 h ( P <0.05),and treatment with RPM significantly down-regulated HMGB1 mRNA expression at 2,6,24 and 48 h following sepsis ( P < 0.05 or 0.01).Meanwhile,pulmonary MPO activity was significantly elevated during 2 h to 48 h observation period,peaked at 24 h ( P < 0.01).Treatment with either AG490 or RPM significantly reduced MPO activity at 24 h and 48 h after CLP ( P <0.05 or 0.01).Conclusion JAK/STAT signaling pathway might be involved in the regulation of pulmonary HMGB1 gene expression after sepsis as a result of peritoneal infection,and inhibition of JAK/STAT could down-regulate HMGB1 mRNA expression in the lung tissue and attenuate CLP-induced acute lung injury.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2004年第5期596-597,共2页
Chinese Journal of Experimental Surgery
基金
国家重点基础研究发展规划项目 (G1 9990 542 0 3)
国家杰出青年科学基金资助项目 (30 1 2 50 2 0 )
全军十五医药卫生科研基金资助项目 (0 1MA2 0 7)
