金雀异黄素预先给药对大鼠机械通气所致肺损伤的作用  

Effect of genistein pretreatment on ventilator-induced lung injury in rats

作　　者：冯丹[1] 姚尚龙[1] 武庆平[1] 王立奎[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院麻醉科,武汉市430022

出　　处：《中华麻醉学杂志》2007年第2期136-139,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金资助项目（30571787）;湖北省科技攻关计划（2005AA301C23）

摘　　要：目的 研究特异性蛋白酪氨酸激酶抑制剂金雀异黄素预先给药对大鼠机械通气所致肺损伤（VILI）的作用。方法 30只健康SD大鼠，随机分为3组，每组10只，A组采用8ml／kg潮气量机械通气；B组采用40ml／kg潮气量机械通气；C组采用40ml／kg潮气量机械通气，并在机械通气前30min腹腔注射金雀异黄素50mg／kg。3组呼吸频率均为80次／min，吸／呼比（I：E）为1：1，PEEP为0，吸人气体为室内空气。机械通气2h后处死大鼠，取肺组织，光镜下观察病理学，测定髓过氧化物酶（MPO）活性、磷酸化p38（p-p38）、p38水平；收集支气管肺泡灌洗液，测定总蛋白、肿瘤坏死因子-α（TNF-α）水平，并进行白细胞（WBC）计数。结果与A组比较，B组支气管肺泡灌洗液总蛋白、WBC计数、TNF-α及肺组织MPO、P—p38／p38水平升高（P〈0．05或0．01），肺组织病理学改变严重；与B组比较，C组上述指标降低（P〈0．01或0．05），肺组织病理学改变明显减轻。结论 金雀异黄素50mg／kg预先给药可减轻大鼠VILI，其机制与抑制了p38通路的激活有关。Objective To investigate the effect of genistein pretreatment on ventilator-induced lung injury （VILI）. Methods Thirty healthy male SD rats were used in this study. The animals were anesthetized with intraperitoneal 20% urethane, tracheotomized, intubated and mechanically ventilated for 2 h. The animals were randomly divided into 3 groups （ n = 10 each） ： group A VT = 8 ml/kg; group B VT = 40 ml/kg and group C VT = 40 ml/kg ＋ genistein. In group C genistein 50 mg/kg was injected intraperitoneally 30 min before mechanical ventilation. The animals were sacrificed by exsanguination at the end of 2 h mechanical ventilation. The lungs were removed for （1） microscopic examination, （2） broncho-alveolar lavage and determination of TNF-α and total protein concentrations in broncho-alveolar lavage fluid （BALF） and （3） determination of p38 and phosphorylated p38 （p-p38） expression and MPO activity in lung tissue. Results Mechanical ventilation with large tidal volume in group B induced serious histopathologic damage and significant increase in TNF-α and total protein concentration＇s in BALF and p-p38 expression and MPO activity in lung tissue as compared with group A. Genistein pretreatment significantly attenuated the changes induced by mechanical ventilation with large VT in group C. Conclusion Genistein 50 mg/kg pretreatment can significantly inhibit the activation of p38 and attenuate VILI.

关 键 词：染料木黄酮 呼吸 人工 呼吸窘迫综合征 成人 

分 类 号：R686[医药卫生—骨科学]