摘要
目的观察羟乙基淀粉130／0．4（万汶）对P38丝裂素活化蛋白激酶（MAPK）信号转导通路的影响，探讨其对感染所致急性肺损伤（Au）保护作用的机制。方法雄性SD大鼠30只，按随机数字表法分为正常对照组、脂多糖（LPS）组（LPS 10mg／kg）、万汶15ml／kg组（LPS 10mg／kg＋羟乙基淀粉130／0．415ml／kg）、万汶30ml／kg组（LPS 10mg／kg＋羟乙基淀粉130／0．430ml／kg）及万汶对照组（羟乙基淀粉130／0．430ml／kg），颈内静脉注入LPS 10mg／kg复制ALI模型。6h后处死大鼠，采集肺脏观察肺组织病理学变化；用蛋白质免疫印迹法（Westernblotting）检测肺组织P—P38、P38、P—P44／42和P44／42的表达；用凝胶电迁移法（EMSA）检测活化蛋白1（AP-1）的DNA结合活性。结果与正常对照组比较，LPS组表现为P38及P44／42的磷酸化水平增高，肺组织AP-1表达上升（P〈0．05或P〈0．01）；万汶15ml／kg和30ml／kg均可抑制LPS导致的P38磷酸化（P均〈0．05），同时可明显抑制AP-1的活性（P均〈0．05）；万汶两个剂量组间比较差异无统计学意义（P均〉0．05）。结论羟乙基淀粉130／0．4通过抑制P38MAPK信号转导通路中P38的磷酸化，进而使其下游的AP-1活性降低，减轻机体炎症反应。
Objective To observe the effect of hydroxyethyl starch 130/0.4 （voluven） on P38 mitogen-activated protein kinases （MAPK） signal transduction pathway, with the aim of investigating the mechanism of its protective effect on acute lung injury （ALI） due to infection. Methods Thirty male Sprague-Dawley （SD） rats were randomly divided into control group, lipopolysaecharide （LPS 10 mg/kg） group, voluven groups （LPS 10 mg/kg, and hydroxyethyl starch 130/0.4 15 ml/kg or 30 ml/kg） and alone voluven group （hydroxyethyl starch 130/0.4 30 ml/kg）, with 6 rats in each group. Rats were sacrificed at 6 hours, the lungs were harvested for observation of pathological changes. The expression of p-P38, P38, p-P44/42 and P44/42 were detected with Western blotting. Activating protein-1 （AP-1） activation was measured with eleetrophoretic mobility shift assay （EMSA）. Results Compared with control, p-P38, p-P44/42 and AP-1 were significantly higher in LPS group （P〈0. 05 or P〈0.01）. The expressions of p-P38 and AP-1 activation were significantly reduced in both voluven groups （all P〈0. 05）. But there was no statistically significant difference between voluven 15 ml/kg and 30 ml/kg groups （all P〈0.05）. Conclusion Hydroxyethyl starch 130/0. 4 can inhibit LPS-indueed ALI by depressing expression of p-P38 and AP-1 activation in lung.
出处
《中国危重病急救医学》
CAS
CSCD
北大核心
2009年第5期270-273,共4页
Chinese Critical Care Medicine
基金
上海市医药卫生“百人计划”基金项目（2003-77-20）
