摘要
目的:观察 Janus 激酶/信号转导和转录激活因子(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)模型,大鼠随机分为正常对照组、CLP 组、JAK2抑制剂(AG490)组和 STAT 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,6～24h 活化达到高峰,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 STAT3。AG490、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<0.05或0.01),肝、肺组织 STAT3活性也显著降低。同时,AG490、RPM 处理组血清 AST、BUN 水平和肺组织 MPO 活性在24～48h 均有不同程度地下降(P<0.05或0.01),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 ac- tivator of transcription(JAK/STAT)pathway and multiple organ dysfunction in rats with sepsis.Methods:Using a sepsis model induced by cecal ligation and puncture(CLP),98 male Wistar rats were randomly divided into nor- mal control group(n=10),CLP group(n=40),AG490(JAK2 inhibitor)treatment group(n=24)and rapamy- cin(RPM,STAT3 inhibitor)treatment group(n=24).At serial time points animals in each group were sacri- ficed,then tissue samples from the liver,lungs,kidneys and small intestine were harvested to detect STAT1/3 ac- tivity,pulmonary myeloperoxidase(MPO)and 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 increased rapidly in the liver,lungs and small in- testine,peaking at 6～24 hours,while their increase was delayed in kidneys.Compared with STAT1,STAT3 ac- tivities 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 decreased STAT1 activities in the liver,lungs as well as small intestine,and STAT3 activities in liver,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 group at 24～48 hours following sepsis(P<0.05 or 0.01).No marked differences in intestinal DAO activity were observed between AG490 or RPM treated group and CLP group(P>0.05).Conclusions:These data suggested that abdominal infection could result in intensive activation of STAT1 and STAT3 in vital organs,and they might play important roles in the pathogenesis of sepsis.Inhibition of JAK/STAT pathway could attenuate multiple organ dysfunction secondary to CLP-induced sepsis in rats.
出处
《感染．炎症．修复》
2003年第3期173-176,共4页
Infection Inflammation Repair
基金
国家重点基础研究发展规划项目(编号 G1999054203)
国家杰出青年科学基金(编号30125020)
军队杰出中青年人才专项基金(编号98J013)
军队十五医药卫生科研基金(编号01MA207)资助项目
关键词
脓毒症
多器官功能损害
信号转导
JAK/STAT
通路
Sepsis
Multiple organ failure
Signal transduetion
Janus kinase/signal transducer and activator of transcription
