蛇床子素对脓毒症急性肺损伤大鼠的保护效应

目的 探讨蛇床子素（Osthole）对脓毒症相关的急性肺损伤大鼠模型的保护效应.方法 采用盲肠结扎穿刺术方法建立急性肺损伤大鼠模型.蛇床子素（100、200 mg/kg）剂量分别处理大鼠模型,24 h后,二辛可宁酸（BCA）测定支气管肺泡灌洗液（BAL）蛋白含量;按不同试剂盒说明测定髓过氧化物酶（myeloperoxidase,MPO）、超氧化物歧化酶（superoxide dismutase,SOD）和丙二醛（malondialdehyde,MDA）的水平;酶联ELISA方法分析细胞因子白介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的水平;Western blot方法检测肺组织活性caspase-3水平.结果 急性肺损伤显著引起BAL蛋白含量的升高[（0.48±0.04）g/L],差异有高度统计学意义（P＜0.01）,在蛇床子素（100、200 mg/kg）处理模型中,BAL蛋白含量则显著下降[（0.33±0.03）、（0.26±0.02 g/L）],差异有统计学意义（P＜0.05）.急性肺损伤模型中肺组织中MPO[（15.651±1.137）U/g wet tissues）]和MDA[（15.568±2.987）nmol/mg protein]水平显著升高（P＜0.05）,而SOD[（9.657±1.237）U/mgprotein]水平下降（P＜0.05）,在蛇床子素（100、200 mg/kg）处理模型中,MPO[（10.884±1.811）、（9.012±0.896） U/g wet tissues]和MDA[（9.345±1.979）、（11.336±1.236） nmol/mg protein]水平显著下降（P＜0.05）,SOD[（14.679±1.035）、（17.639±1.893）U/mgprotein]水平显著升高（P＜0.05）.炎症因子IL-6和TNF-α水平在急性肺损伤模型中显著升高（P＜0.05）,在蛇床子素（100和200 mg/kg）处理模型中水平受到显著抑制（P＜0.05）.Western blot结果显示急性肺损伤模型中,活性caspase-3水平升高,而在蛇床子素处理模型其水平显著下降.结论 蛇床子素能够抑制炎性反应,缓解肺组织的氧化应激反应,降低肺部细胞的凋亡,从而减轻肺组织的损伤和通透性的变化,对急性肺损伤大鼠有显著的保护效应,其作用效果和机制值得深入研究和探讨.

The protective effect of Osthole in rats with sepsis-induced acute lung injury

Objective To investigate the effect of Osthole in rats with sepsis-induced acute lung injury.Methods Rats model of sepsis-induced acute lung injury were established by cecum ligation puncture.Different dose of Osthole （100 and 200 mg/kg） was administrated and after 24 h,total protein levels in BAL were measured via BCA method; levels of MPO,SOD and MDA were detected according protocols of different kits; levels of cytokines,IL-6 and TNF-α,were determined by ELISA method.Activated caspase-3 level was analyzed by Western blot.Results The total protein level of BAL increased in acute lung injury （ALI） models [（0.48±0.04）g/L] with statistically significant difference （P ＜ 0.01） and decreased to （0.33±0.03） g/L （100 mg/kg） and （0.26±0.02） g/L （200 mg/kg） in Osthole treatment models （P ＜ 0.05）.The levels of MPO [（15.651±1.137）U/g wet tissues）] and MDA [（15.568±2.987） nmol/mg protein] highly increased in ALI models （P ＜ 0.05）,and SOD decreased significantly [（9.657±1.237） U/mg protein] （P ＜ 0.05）,and also significantly decreased in Osthole treatment models [MPO：（10.884± 1.811）,（9.012±0.896） U/g wet tissues; MDA：（9.345±1.979）,（11.336±1.236） nmol/mg protein]; and SOD increased significantly [（14.679±1.035）,（17.639±1.893） U/mg protein] with statistically significant difference （P ＜ 0.05）.Pro-inflammation cytokines IL-6 and TNF-α which were highly up-regulated in ALI models,and were significantly down-regulated in Osthole treatment models （P ＜ 0.05）.Caspase-3 which was activated in ALI models was down-regulated in Osthole treatment group.Conclusion Osthole shows protective effects for rats with sepsis-induced acute lung injury through suppression of inflammatory reaction,remission of oxidative stress,inhibition of cell apoptosis of which the effects and underlying mechanisms deserve further investigated.