合成肽S247 预先给药对大鼠呼吸机相关性肺损伤与影响.docVIP

合成肽S247预先给药对大鼠呼吸机相关性肺损伤的影响 华中科技大学同济医学院附属协和医院麻醉科，武汉 430022 桂平 武庆平 姚尚龙 【摘要】 目的 研究合成肽S247预先给药对大鼠呼吸机相关性肺损伤（VILI）的影响及其机制。方法 24只雄性SD大鼠随机分为3组（n=8），对照组（C组）：不进行机械通气；高潮气量组（H组）：潮气量40ml/kg，呼气末正压0 cmH2O ，呼吸频率40次/min，吸入氧浓度21％；S247预先给药组（S组）：腹腔注射S247 100mg.kg-1.d-1 1次/d，持续2周，在最后一次注射30min后开始机械通气，机械通气的参数设定同H组。C组和H组在相同的时间点注射等量的生理盐水。机械通气4h后放血处死大鼠，取肺组织，光镜下观察肺病理变化，测定肺湿/干重比（W/D），免疫组化检测转化生长因子-β1（TGF-β1）的表达；收集支气管肺泡灌洗液（BALF），测定总蛋白（TP）含量、肿瘤坏死因子α（TNF-α）和巨噬细胞炎性蛋白2（MIP-2）的浓度，并进行白细胞（WBC）计数。 结果 与C组比较，H组和S组W/D、WBC计数、TP含量和TGF-β1的表达升高（P0.01），H组MIP-2的浓度升高(P0.01)并且肺组织病理学改变严重；与H组比较，S组W/D、WBC计数、TP含量、TNF-α和MIP-2浓度和TGF-β1的表达降低(P0.01或0.05)，肺组织病理学改变明显减轻。结论 S247预先给药可减轻大鼠VILI，其机制与抑制了TGF-β1的激活有关。 【关键词】 呼吸窘迫综合征，成人；呼吸，人工；转化生长因子-β1 Effect of synthesized peptide S247 pretreatment on ventilator-induced lung injury in rats WU Qing-ping Department of Anesthesiology , Union Hospital , Tongji Medical College , Huangzhong University of Science and Technology , Wuhan 430022 , China 【Abstract】 Objective To investigate the effect of synthesized peptide S247 pretreatment on ventilator-induced lung injury(VILI) and its possible mechanism . Methods Twenty four male SD rats weighing 250-313g were randomly divided into 3 group(n=8 each) : control group(group C): no mechanical ventilation; high tidal volume group(group H): 40ml/kg tidal volume , 0 cmH2O of positive end-expiratory pressure , 40 breaths/min and FiO2=0.21; S247 pretreatment group(group S): Rats in group S received intraperitoneal injection of S247 one time every day(100mg.kg-1.d-1) and the treatment lasted for two weeks . Mechanical ventilation started 30min after the last injection and mechanical ventilation settings were the same as group H .Rats in group C and group H were injected with equal volume of normal saline at the same time . The animals were sacrificed by exsanguination at the end of 4h mechanical ventilation . The lungs were removed for (1) microscopic examination , measuring wet-to-dry weight ratios(W/D) and determination of transforming gro