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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 observe the activation of Janus kinase / signal transducer and activator of transcription (JAK / STAT) pathway in sepsis rats induced by intraperitoneal infection and its relationship with multiple organ dysfunction. Methods: The cecal ligation and puncture (CLP) model was used. The rats were randomly divided into normal control group, CLP group, JAK2 inhibitor (AG490) group and STAT inhibitor (rapamycin, RPM) group. The activities of STAT1 / 3 in liver, lung, kidney and intestine were determined. The contents of AST and BUN, the activities of myeloperoxidase (MPO) and diamine oxidase (DAO) RESULTS: STAT1 in liver, lung and intestine rapidly activated at 2h after CLP, and peaked at 6 ~ 24h, while activation of STAT1 in renal tissue was relatively slow. STAT3 activity in liver and lung tissues also increased significantly, but no activated STAT3 was detected in kidney and intestinal tissues. After AG490 and RPM treatment, the activities of STAT1 in other tissues decreased to some extents (P <0.05 or 0.01), and the activities of STAT3 in liver and lung decreased significantly after the early treatment. At the same time, serum AST, BUN levels and MPO activity in lung tissue of AG490 and RPM groups decreased to different extents (P <0.05 or 0.01) in 24-48h, but the activity of DAO in small intestine did not change significantly. Conclusion: STAT1 and STAT3 are highly activated in sepsis and are involved in the pathological process of sepsis caused by severe abdominal infection. Inhibition of JAK / STAT pathway activation contributes to the prevention and treatment of multiple organ dysfunction.