JAK抑制剂AG490对大鼠组织iNOS和NO合成的影响  

Effects of janus kinase/signal transducer and activator of transcription pathway on synthesis of iNOS and NO in pulmonary and vascular tissues of infectious shock rats

作　　者：王松柏[1] 裴树俊[1] 徐昌富[2] 李海[1] 

机构地区：[1]解放军251医院麻醉科,张家口075000 [2]解放军251医院心胸外科,张家口075000

出　　处：《第三军医大学学报》2007年第15期1511-1513,共3页Journal of Third Military Medical University

摘　　要：目的观察JAK/STAT通路对脓毒症大鼠组织和血清诱导型一氧化氮合成酶(iNOS)和一氧化氮(NO)合成的影响。方法采用盲肠结扎穿孔术(cecal ligation puncture,CLP)制造大鼠脓毒症模型,将48只Wistar大鼠随机分为正常对照组、假手术组、CLP脓毒症组和AG490处理组。分别采集正常对照组、假手术组以及CLP组和AG490组2、6、24h的组织和血清,采用RT-PCR测定组织iNOS mRNA表达水平,NO检测试剂盒(酶法)检测组织和血清NO含量;同时分别监测上述各时间点的平均动脉压、脉搏。结果正常组大鼠血清、肺和血管含有少量iNOS mRNA和NO,与正常组大鼠相比,假手术组iNOS mRNA和NO的含量均未见明显差别,CLP后各时间点肺、血管和血清iNOS mRNA、NO含量均升高明显;而MAP严重下降、脉搏剧烈升高(P<0.05,P<0.01)。AG490处理组与CLP组相应时间点相比,肺、血管和血清多个时间点iNOS mRNA表达和NO含量均显著下降;血压和脉搏均显著好转(P<0.05,P<0.01)。相关分析显示:肺和血管组织NO与iNOS mRNA的相关系数分别是0.75和0.73;血清与NO与肺、血管组织iNOS mRNA的相关系数分别是0.68和0.62(P<0.05),MAP与肺、血管和血浆NO的相关系数分别是-0.85、-0.86和-0.91(P<0.05)。结论抑制JAK/STAT通路活化可抑制脓毒症大鼠血浆和组织iNOS mRNA和NO合成;并改善循环功能。Objective To determine the effects of janus kinase/signal transducer and activator of transcription on the synthesis of inducible nitric oxide synthase （iNOS） and nitric oxide （NO） in infectious shock rats. Methods Forty-eight male Wistar rats were randomly divided into normal control, sham operation group, cecal ligation puncture （CLP） group, and inhibitor of JAK （AG490） treatment group. CLP group and AG490 group were established into the sepsis model induced by CLP, and at 2, 6, 24 h after CLP, the rats were sacririced. The pulmonary, vascular tissues and serum samples of all rats were harvested to determine iNOS mRNA expression levels by reverse transcription polymerase chain reaction （RT-PCR） and NO content respectively. Meanwhile, the mean arterial pressure （MAP） and pulse were monitored. Results No notable difference was detected in all parameters between sham operation group and normal control. Compared with normal control, iNOS mRNA and NO levels in pulmonary, vascular tissues and serum at 2, 6 and 24 h following CLP significantly elevated respectively, and MAP fell notably and pulse increased （P 〈 0.05 or 0.01 ）. AG490 treatment decreased iNOS mRNA and NO levels markedly at 2 or 6 h after CLP, meanwhile MAP and pulse deteriorated by sepsis were also ameliorated （ P 〈 0.05 or 0.01 ）. Conclusion Inhibiting the activation of JAK/STAT pathway can reduce tissues and serum iNOS mRNA and NO expressions in infectious shock rats and can ameliorate the circulatory function deteriorated by sepsis.

关 键 词：Janus激酶抑制剂/AG490 NO 脓毒症 JAK/STAT信号通路 大鼠 INOS 

分 类 号：R362[医药卫生—病理学] R631.02[医药卫生—基础医学]