摘要
目的探讨Janus激酶/信号转导和转录激活子(janus kinase/signal transducer and activator of transcription,JAK/STAT)通路对严重腹腔感染肝、肺中干扰素-γ(interferon-,γIFN-γ)表达的调节作用。方法采用盲肠结扎穿孔(CLP)模型,大鼠分为CLP组、JAK激酶抑制剂(AG490)处理组和STAT抑制剂(RPM)处理组。采用RT-PCR技术和ELISA检测试剂盒检测肝、肺IFN-γmRNA表达水平和蛋白含量。结果与CLP 0时相点相比,CLP后各时相点IFN-γmRNA表达水平和蛋白含量不同程度升高(P<0.05,P<0.01)。经JAK和STATA抑制剂预处理后,与CLP组相应时相点相比,CLP后多个时相点IFN-γmRNA表达水平和蛋白含量显著下降(P<0.05,P<0.01)。结论腹腔脓毒症时肝、肺IFN-γ表达明显升高,抑制JAK/STAT通路的活化可下调肝、肺IFN-γ的表达,这可能是防止及治疗多器官功能衰竭的一个新的干预途径。
Objective To determine the effect of janus kinase/signal transducer and activator of transcription （JAK/STAT） pathway on the expressions of interferon-γ （IFN-γ） in vital organs of rats with sepsis. Methods A sepsis model was induced by cecal ligation puncture （CLP） in 60 male Wistar rats, and randomly divided into CLP group （ n = 24）, AG490 group in which inhibitor of JAK-AG490 at dose of 8 mg/kg was subcutaneously injected 30 min before CLP （n = 18）, and rapamycin group in which inhibitor of STAT-rapamycin at dose of 0.4 mg/kg was subcutaneously injected 30 min before CLP （n = 18）. On 2, 6, 24 h after CLP, all rats were sacrificed, then hepatic and pulmonary tissue samples were harvested to determine IFN-γmRNA expression levels by reverse transcription polymerase chain reaction （RT-PCR） and its protein expression levels by enzyme-linked immunosorbent assay （ELISA）. Results As compared with normal rats without CLP, IFN-γ mRNA and protein levels in hepatic and pulmonary tissues at 2, 6, 24 h after CLP significantly elevated （P 〈 0.05, P 〈0.01 ）. AG490 or rapamycin could markedly reduce IFN-γmRNA and protein expression levels at 2 or 6 h after CLP （P 〈0.05, P〈0.01 ）. Conclusion Our data suggest that severe intra-abdominal infection can elevate IFN-γexpressions in vital organs, which might be involved in JAK/STAT pathway. Inhibiting the activation of JAK/STAT pathway can reduce IFN-γexpressions.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2006年第15期1585-1587,共3页
Journal of Third Military Medical University
