环氧化酶2抑制剂对大鼠机械通气所致肺损伤肺水代谢的影响  

Effect of cyclooxygenase 2 inhibitor on pulmonary water metabolism of ventilator-induced lung injury in rats

作　　者：金立达[1] 王良荣[1] 熊响清[1] 林丽娜[1] 单鸳露[1] 

机构地区：[1]温州医学院附属第一医院麻醉科,浙江温州325000

出　　处：《温州医学院学报》2013年第1期38-40,共3页Journal of Wenzhou Medical College

基　　金：温州市科技局科研基金资助项目(Y20100025)

摘　　要：目的:探讨环氧化酶2(COX-2)抑制剂对大鼠机械通气所致肺损伤(VILI)肺水代谢的影响。方法:健康成年雄性SD大鼠30只,体质量300～350 g,随机分为3组(n=10),对照组(TV组,潮气量8 mL/kg)、机械通气肺损伤组(HV组,潮气量40 mL/kg)、NS398预处理组(HV+NS398组)。NS398预处理组于机械通气前30 min腹腔注射COX-2抑制剂NS398 8 mg/kg。于机械通气4 h时处死大鼠,West-ern Blot法检测肺组织中水通道蛋白1(AQP1)、水通道蛋白5(AQP5)表达;检测血清及支气管肺泡灌洗液(BALF)中蛋白浓度,计算肺通透性指数(LPI);检测BALF中肿瘤坏死因子(TNF-α)浓度;计算肺组织湿/干重比(W/D)。结果:与TV组相比,HV组BALF中TNF-α浓度增加,AQP1、AQP5表达降低(P<0.05),LPI升高,肺组织W/D升高(P<0.05);与HV组相比,HV+NS398组BALF中TNF-α浓度降低,AQP1、AQP5表达升高(P<0.05),LPI及肺组织W/D降低(P<0.05)。结论:COX-2抑制剂可能通过上调AQP1、AQP5的表达,减轻肺水肿改善肺水代谢,从而减轻大鼠机械通气所致肺损伤。Objective： To investigate the effect of cyclooxygenase 2 inhibitor on pulmonary water metabo-lism of ventilator-mduced lung injury m rats. Methoas： Thirty healthy adult male 5D rats weighing 300-330 g were randomly divided into 3 groups （n =10 each）： group TV （traditional tidal volume VT=8 mL/kg）; group HV （high tidal volume VT=40 mL/kg） and group HV＋NS398 （pretreated with NS398 8 mg/kg before ventilation）. The animals were anesthe-tized with intraperitoneal 20% urethane 8 mL/kg, tracheotomized, intubated and mechanically ventilated for 4 h. Group HV＋NS398 8 mg/kg was intraperitoneally injected at 30 min before mechanical ventilation. The animals were sacrificed at 4 h after mechanical ventilation. The lungs were removed for determination the concentration of protein in bronchoalveolar lavage fluid （BALF）, TNF- ct concentration, lung permeability index （LPI） and wet to dry weight ratio （W/D）. Expression of aquaporin 1 （AQP1） and aquaporin 5 （AQP5） was analyzed with Western blot. Results： The BALF concentration of TNF- （x and ex- pression of AQP1 and AQP5 decreased significantly in group HV than that in group TV. The LPI and W/D were higher in group HV than that in group TV. Cyclooxygenase-2 inhibitor significantly attenuated the HV-induced changes listed above in group HV＋NS398. Conclusion： Cyclooxygenase 2 inhibitor attenuates ventilation- induced lung injury in rats. Its mechanism may relate to upregulate expression of aquaporin 1 and aquaporin 5, strengthen the active reabsorption and exchange of fluid between alveolar space and alveolar epithelium barrier during edema in VILI.

关 键 词：环氧化酶2抑制剂 呼吸 人工 呼吸窘迫综合征 成人 水通道蛋白 大鼠 

分 类 号：R965[医药卫生—药理学]