Src激酶／信号转导子与转录活化子信号转导通路对内毒素致大鼠急性肺损伤的影响  

The influence of src kinase/signal transducer and activator of transcription on lipopolysaccharide-induced acute lung injury in rats

作　　者：朱珊珊[1] 焦皓[1,2] 封光[1,2] 刘功俭[1,2] 

机构地区：[1]徐州医学院江苏省麻醉重点实验室&江苏省麻醉重点研究所,221002 [2]徐州医学院附属医院麻醉科

出　　处：《国际麻醉学与复苏杂志》2012年第8期533-537,共5页International Journal of Anesthesiology and Resuscitation

基　　金：基金项目：江苏省高校自然科学研究指导性项目（11KJD3200030）

摘　　要：目的研究Src激酶信号转导子与转录活化子（srckinase／signaltransducerandactivatoroftranscription，Src／STAT）信号转导通路在内毒素脂多糖（1ipopolysaccharide，LPS）致急性肺损伤（acutelunginjury，Au）中的作用。方法60只雄性SD大鼠使用随机数字表将其分成4组，即空白对照组（NS）组、内毒素脂多糖（IJPs）组、LPS＋SU6656（LPS＋SU）组和NS＋SU6656（NS＋SU）组。双抗体夹心酶联免疫吸附法（ELISA法）检测不同时间点大鼠支气管肺泡灌洗液（bronchoalveolarlavagefluid，BALF）中巨噬细胞炎症蛋白-2（macrophageinflammatoryprotein2，MIP-2）和白细胞介素（IL）-6的浓度，HE染色检测肺组织病理学变化，蛋白质印记分析法（westernblot法）检测肺组织中磷酸化STAT、核因子一KB（nuclearfactorkappaB，NF—KB）和NF—KB抑制蛋白（IRBoL）的表达。另取40只雄性SD大鼠，使用同上的方法随机分成4组，分组同上，比较其生存率。结果LPS组大鼠肺部炎症和肺损伤明显，与LPS组比较，BALF中MIP-2和IL-6降低[MIP-2，6h达高峰：（1135±209）VS（875±112），（P〈0．05）；IL-6，3h达高峰（2235±267）vs（5125±658），（P〈0．05）]；病理切片示肺组织损伤程度较轻；肺组织湿／干重比降低【（4．3±0．2）VS（5．6±0．4）】（P〈O．05）；48h生存率提高（37．6％VS10．5％，P〈0．05）；肺组织NF-KB活化及胞浆中IKBtx的降解均受抑制。结论以上数据表明，Src／STAT信号通路在LPS诱导的Au中发挥重要作用，Src激酶特异性抑制剂（SU6656）可抑制NF-KB的活化和IKBot的降解，提示Src／STAT通路的活化可能参与NF-KB的活化过程。Objective To investigate the role of Src/STAT signal pathway in LPS-induced ALI. Methods Sixty male SD rats were divided into four groups using a random number table： blank （NS） group, lipopolysaccharide （LPS） group, LPS＋SU6656 （LPS＋SU） group and NS＋SU6656 （NS＋SU） group. The concentrations of macrophage inflammatory protein 2（MIP-2） and interleukin （IL）-6 in bronchoalveolar lavage fluids （BALF） were detected by ELISA and the histopathologic changes of lung tissues were observed by hematoxylin-eosin （H-E） staining. The expression of nuclear factor kappa B（NF-KB） in nuclear extracts, phosphor-STAT and IKBct in cytoplasmic extracts were analyzed by Western blot. In addition, survival rate with the other 10 rates each group was investigated. Results The serious pulmonary inflammation and conspicuous lung damage were observed in LPS group. AS compared with LPS group, the MIP-2 and IL-6 in BALF were significantly decreased [MIP-2 reached a peak at 6 h, （ 1 135±209） vs （ 875± 112）, P〈0.05. IL-6 reached a peak at 3 h, （2 235±267 ） vs （5 125 ±658 ）, P〈0.05]. The histopathologic changes of lung tissues were relieved obviously. Wet / dry weight ratio of the lung was decreased. LPS＋SU6656 group had a higher survival rate （37.6% vs 10.5% ,P〈0.05） and the NF-κB activation and the degradation of IKBα in cytoplasma were inhibited. Conclusions These data suggested that Src/STAT signal pathway plays an essential role in LPS-induced acute lung injury. SU6656, Src kinase specific inhibitor, attenuates LPS-induced lung injury via inhibiting the NF-KB activation and IKBα degradation, indicating that the Src/STAT signal pathway may be involved in the activation of NF-KB.

关 键 词：Src激酶/信号转导子与转录活化子信号通路 脂多糖 急性肺损伤 核因子-ΚB SU6656 巨噬细胞炎症 蛋白-2 自细胞介素缶 

分 类 号：R285.5[医药卫生—中药学]