严重腹腔感染大鼠JAK/STAT通路活化与多器官功能损害的关系  

Relationship between activation of Janus kinase/signal transducer and activator of transcription pathway and multiple organ dysfunction in rats with sepsis

作　　者：王松柏[1] 姚咏明[1] 陈劲松[2] 董宁[1] 于燕[1] 盛志勇[1] 

机构地区：[1]解放军第304医院全军烧伤研究所,北京100037 [2]解放军第187医院

出　　处：《解放军医学杂志》2004年第1期42-44,共3页Medical Journal of Chinese People's Liberation Army

基　　金：国家重点基础研究发展规划项目 (编号G1 9990 542 0 3);国家杰出青年科学基金 (编号 30 1 2 50 2 0 );军队杰出中青年人才专项基金 (编号98J0 1 3);军队十五医药卫生科研基金 (编号 0 1MA2 0 7)资助课题

摘　　要：目的　观察Janus激酶 /信号转导子和转录激活因子 (JAK/STAT )通路在腹腔感染所致脓毒症大鼠组织中的活化规律及其与多器官功能损害的关系。方法　采用盲肠结扎穿孔 (CLP)法制作大鼠脓毒症模型。大鼠随机分为正常对照组、CLP组、JAK 2抑制剂 (AG4 90 )组和STAT 3抑制剂 (雷帕霉素 ,RPM)组。留取肝、肺、肾、肠组织测定STAT1/ 3活性 ,同时测定血清AST、BUN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后 2h肝、肺、肠组织中STAT1均迅速活化 ,6～ 2 4h达高峰 ,而肾组织STAT1活化相对迟缓。肝、肺组织中STAT3活性亦明显升高 ,但肾、肠组织中未检测到活化的STAT 3。AG4 90、RPM早期处理后 ,除肾组织外 ,其他组织STAT1活性均有不同程度下降 (P <0 0 5或 0 0 1) ,肝、肺组织STAT3活性也显著降低。同时 ,AG4 90、RPM处理组血清AST、BUN水平和肺组织MPO活性在 2 4～ 4 8h均有不同程度下降 (P <0 0 5或 0 0 1) ,但小肠DAO活性无明显改变。结论　STAT1、STAT3在脓毒症时高度活化 ,并参与了严重腹腔感染所致脓毒症的病理过程。抑制JAK/STAT通路活化有助于多器官功能损害的防治。Objective To investigate the relationship between activation of Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and multiple organ dysfunction in rats with sepsis. Methods Using a sepsis model produced by cecal ligation and puncture (CLP), 98 male Wistar rats were randomly divided into normal control group (n=10), CLP group (n=40), AG490 (JAK2 inhibitor) treatment group (n=24) and rapamycin (RPM, STAT3 inhibitor) treatment group (n=24). At serial time points, the animals in each group were sacrificed, then tissue samples from the liver, lungs, kidneys and small intestine were harvested to detect STAT1/3 activity, pulmonary myeloperoxidase (MPO) and small intestinal diamine oxidase (DAO) activities. Meanwhile, organ function parameters including serum aspartate transaminase (AST) and blood urea nitrogen (BUN) contents were also measured. Results At 2 hours after CLP, STAT1 activities were found to be enhanced rapidly in the liver, lungs and small intestine, peaking at 6-24 hours, but their increase was delayed in the kidneys. Compared with STAT1, STAT3 activities were weaker and detected only in the liver and lungs, with no detectable STAT3 in the small intestine and kidneys. Pretreatment with either AG490 or RPM significantly lowered STAT1 activities in the liver, lungs and small intestine as well as STAT3 activities in the liver and lungs (P<0.05 or 0.01). In addition, serum AST, BUN contents and pulmonary MPO activity were significantly reduced in AG490 and RPM treated groups compared with those in CLP treated group at 24-48 hours following sepsis (P<0.05 or 0.01). No marked differences were observed between AG490 or RPM treated group and CLP group in intestinal DAO activity(P>0.05). Conclusions These data suggest that abdominal infection can result in intensive activation of STAT1 and STAT3 in vital organs, and they play important roles in the pathogenesis of sepsis. Inhibition of JAK/STAT pathway can attenuate multiple organ dysfunction secondary to CLP-induced sepsis in r

关 键 词：脓毒症 多器官功能衰竭 信号传递 Janus激酶/信号转导子和转录激活因子 

分 类 号：R631.02[医药卫生—外科学]