中文摘要：

目的探讨Janus激酶／信号转导和转录激活因子（JAK／STAT）通路对盲肠结扎穿孔术（CLP）所致脓毒症大鼠多器官高迁移率族蛋白B1（HMGBl）基因表达的影响及其意义。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（60只）、JAK2抑制剂AG490干预组（24只）、STAT抑制剂雷帕霉素（RPM）干预组（24只）。留取肝、肺、肾、肠组织测定HMGB1mRNA表达和STAT1／3的DNA结合活性。结果CLP后，肝、肺、肾、肠组织中STATl在脓毒症早期即迅速活化，6-12h后活化达高峰。肝、肺组织中STAT3的活化特点与STAT1相似，但相对较弱；在肾、肠组织中未探测到STAT3的活化。同时，CLP组除肾组织HMGB1mRNA表达改变不明显外，肝、肺、肠组织其表达均明显增强（P＜0．05或P＜0．01）。AG490早期处理后24—48h，肝、肠组织HMGB1mRNA表达显著低于CLP组（P＜0．05或P＜0．01）；RPM干预组肝、肺、肠组织HMGB1mRNA表达均呈现不同程度地抑制，其中以肺组织下降幅度尤为明显。结论严重腹腔感染可导致机体主要脏器JAK／STAT通路迅速活化，该信号途径参与了HMGB1mRNA的表达调控过程。

英文摘要：

Objective To investigate the potential role of Janus kinase/signal transducer and activator of transcription （JAK/STAT） pathway in regulation of gene expression of high mobility group box-1 protein （HMGB1） in various tissues in rats with sepsis. Methods A sepsis model reproduced by cecal ligation and puncture （CLP）, and 128 male Wistar rats were randomly divided into normal control group （ n = 10）, sham operation group （ n = 10）, CLP group （ n = 60）, AG490 treatment group （ n = 24）, and rapamycin （RPM） treatment group （ n = 24）. At serial time points animals in each group were sacrificed after CLP, then tissue samples were harvested to determine HMGB1 mRNA expression and STAT1/3 DNA binding activity. Results STAT1 activities increased rapidly in the liver, lungs and small intestine after CLP, peaking at 6-12 h, while it increased slowly, and still kept at mild level from 2 to 48 h in the kidneys. Compared with STAT1, lower STAT3 activities were detected only in the liver and lungs, with negative detection in the small intestine and kidneys. HMGB1 mRNA levels significantly increased in liver, lungs and small intestine at various time points after CLP respectively （ P〈0.05 or P〈0. 01 ）, while they didn＇t change in the kidneys. Treatment with AG490 could markedly inhibit HMGB1 mRNA expression in the liver and small intestine at 24 and 48 h （P 〈0. 05 or P〈0. 01 ）, and in lungs at 2 h following CLP （P〈0.01 ）. Similarly, treatment with RPM significantly decreased HMGB1 mRNA expression in the lungs at 2, 6, 24 and 48 h, in the liver at 6 and 24 h, and in the small intestine at 24 and 48 h （P〈0. 05 or P〈0.01 ）. In addition, STAT1 and STAT3 activities in the liver and lungs were significantly correlated with corresponding tissue HMGB1 mRNA expression. Conclusions Peritoneal infection could extensively activate STAT1 and limitedly activate STAT3 in vital organs. Activation of JAK/STAT pathway might be involved in up-regulatingthe gene expression of HMGB1 a