摘要
目的:由于缺乏有效、特异性的治疗,急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)的病死率居高不下,丙酮酸乙酯作为新的抗炎药物,能拮抗致死性脓毒症和系统性炎性反应。实验观察丙酮酸乙酯对油酸诱导ALI大鼠肺的早期保护作用及其可能的机制,为脂肪栓塞综合征诱导肺损伤提供新的治疗方案。方法:清洁级雄性SD大鼠18只,随机分为对照组、ALI组和治疗组,每组6只。ALI组大鼠经颈静脉注射油酸0.15 ml/kg,造成肺损伤模型。治疗组大鼠在造模后,腹腔注射丙酮酸乙酯40 mg/kg,4 h后放血处死动物,留取血液标本,用ELISA法测血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、血管假性血友病因(vWF)表达,取肺组织测定肺通透性指数(PPI)、肺血管外肺水量(EVLW)和肺湿质量与干质量比值(W/D)。Western blotting检测肺组织丝裂原活化蛋白激酶(ERK1/2、P38和JNK MAPK)磷酸化蛋白表达。结果:①病理生理表现提示,试验动物造模成功。②与ALI组比较,治疗组大鼠肺组织病理损伤明显减轻。③ALI组PPI、EVWL、W/D显著高于对照组(P<0.01)和治疗组(P<0.01)。④ALI组TNF-α、IL-6和vWF血清含量显著高于治疗组(P<0.01)和对照组(P<0.01)。⑤与对照组相比,ALI组ERK1/2、P38 MAPK的磷酸化表达显著增加。与ALI组相比,治疗组ERK1/2、P38 MAPK的磷酸化表达明显降低,但仍高于对照组。各组间JNK MAPK磷酸化表达差异无显著性统计学意义。结论:丙酮酸乙酯明显抑制细胞内信号转导蛋白ERK1/2、P38 MAPK的磷酸化表达,下调TNF-α、IL-6等炎性介质的水平,减少肺微血管清蛋白的通透性,减轻血管内皮细胞的损伤,对油酸诱导的ALI有显著的肺保护作用。
Objective：Lock of specific and efficient therapy leads to the high mortality rate of acute lung injury（ALI） and acute respiratory distress（ARDS）.Ethyl pyruvate as a novel anti-inflammatory agent,protects against lethal sepsis and systemic inflammation.To observe the effects of ethyl pyruvate（EP） treatment on oleic acid-induced ALI in rats,and investigate the mechanisms of its protective effect. Methods：16 SD rats were randomly divided into three equal groups namely： normal control group,oleic acid-induced lung injury group（OA-group） and EP-treatment group（EP-group）.OA-group was administered oleic acid（0.15ml/kg） via right jugular vein.In EP-group,40mg/kg was injected intraperitoneally,followed 10min later by OA infusion.At the 4 hours animals were sacrificed.Human serum albumin（Alb） labeled with 125I（125I-Alb,6ml/Kg） were infused over 1min via right jugular vein exactly 1 hour before the rats were sacrificed.Serum TNF-α、IL-6、VWF were determined by ELISA.The lungs were harvested to measure pulmonary permeability index（PPI）,extravascular lung water（EVLW） and lung wet/dry ratio.The expressions of lung tissue mitogen-activated protein kinase（ERK1/2,P38 and JNK MAPK） were analysed by Western blotting.Results： Rats had significantly improved lung histopathology in EP-group compared to OA-group.The PPI、EVWL、W/D of OA-group were significantly higher than that of normal control group（P〈0.01） and EP-group（P〈0.01）.OA-group significantly increased the concentration of these cytokines（TNF-α、IL-6、VWF）（P〈0.01） in serum.The lung tissue levels of phospho-ERK1/2 and phospho-P38 MAPK expressions were markedly higher in all group compared to heparin treatment group.There were no markedly differences of phospho-JNK MAPK expression in three groups.Conclusion： Ethyl Pyruvate markedly inhibited the expressions of phospho-ERK12 and phospho-P38 MAPK,down-regulated the inflammatory reaction and significantly improved lung injury in oleic acid-induced
出处
《医学研究生学报》
CAS
2009年第4期368-371,375,I0001,共6页
Journal of Medical Postgraduates
基金
南京军区南京总医院科研基金资助项目(批准号:Z2008014)
