目的 研究Src激酶/信号转导子与转录活化子(src kinase/signal transducer and activator of transcription, Src/STAT)信号转导通路在内毒素脂多糖（lipopolysaccharide, LPS）致急性肺损伤（acute lung injury, ALI）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(LPS)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(bronchoalveolar lavage fluid, BALF)中巨噬细胞炎症蛋白-2(macrophage inflammatory protein 2, 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（Western blot法）检测肺组织中磷酸化STAT、核因子-κB (nuclear factor kappa B , NF-κB)和NF-κB抑制蛋白( IκBα)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, 6 h达高峰: (1 135±209) vs.(875±112),(P<0.05)；IL-6, 3 h达高峰(2 235±267) vs (5 125±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 （5.56±0.36）], (P<0.05)；48 h生存率提高(37.6%vs10.5%, P<0.05)；肺组织NF-κB活化及胞浆中IκBα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ALI中发挥重要作用，Src激酶特异性抑制剂(SU6656)可抑制NF-κB的活化和IκBα的降解，提示Src/STAT通路的活化可能参与NF-κB的活化过程。
Objective To investigate the role of Src/STAT signal pathway in LPS-inducedALI. 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-κB) in nuclear extracts, phosphor-STAT and IκBα 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 6h, 1135±209 vs.875±112,p<0.05;IL-6 reached a peak at 3h, 2235±267 vs.5125±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 IκBα 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-κB activation and IκBα degradation, indicating that the Src/STAT signal pathway may be involved in the activation of NF-κB.
Cited
)
