丙泊酚对呼吸机所致肺损伤促分裂原活化蛋白激酶活化及炎症反应的影响

Effects of propofol on activation of p38MAPK in rat model with ventilator-induced lung injury

目的探讨丙泊酚对呼吸机所致肺损伤大鼠肺部促分裂原活化蛋白激酶和炎症反应的影响。方法 SD大鼠随机均分成3组:常规潮气量通气组(C组)、大潮气量通气组(H组)和丙泊酚处理组(P组)。P组在大潮气量通气同时给予丙泊酚,C组和H组给予生理盐水。收集肺灌洗液和组织标本,测量肺组织湿/干比,观察肺病理改变,检测支气管肺泡灌洗液中总蛋白、白介素1β(IL-1β)和白介素6(IL-6)的含量,Western blot方法检测各组肺组织中促分裂原活化蛋白激酶和磷酸化水平。结果 C组大鼠肺部未见明显的病理改变,H组和P组肺部有明显的病理改变,而P组大鼠肺部病理改变较H组明显减轻;H组和P组肺组织湿/干比、p-p38、支气管肺泡灌洗液中白细胞总数、总蛋白含量、IL-1β和IL-6水平明显高于C组,上述指标P组明显低于H组。结论丙泊酚能够减轻大潮气量机械通气造成的大鼠肺损伤,其机制可能部分与阻断促分裂原活化蛋白激酶活化以及肺部炎症有关。

Objective To elucidate the effects of propofol on the phosphorylation of mitogen activated protein kinase（p38MAPK） and inflammatory lung injury in arat model of ventilator-induced lung injury（VILI）. Methods Sprague-Dawley rats were randomized to three groups： standard ventilation group（Group C）,high-tidal volume ventilation group（Group H）,and high-tidal volume ventilation plus propofol group（Group P）.During mechanical ventilation（MV）,rats in Group P received intravenous propofol,while rats of group C and H received physiological saline instead.All rats were sacrificed for collection of lung lavage fluid and lung tissue.Lung wet and dry weight ratio（W/D） was calculated,and lung pathologic changes were observed under light microscope.Interleukin 1β（IL-1β）,IL-6 and total protein in bronchoalveolar lavage fluid（BALF） were determined.The expression of p38 and p-p38 was measured by Western blot. Results No pulmonary pathologic change was observed in Group C.Although pathological changes were observed in Group H and P,significantly milder changes were revealed in Group P.Significant step-down of pulmonary W/D,WBC count in p-p38 and BALF,total protein content,and IL-1β and IL-6 levels was observed following the sequencing of Group H,P and C. Conclusion Propofol attenuates VILI in rats,via blocking the activation of extracellular regulated protein and reducing pulmonary inflammation.