环氧合酶-2抑制剂对大鼠机械通气所致肺损伤的影响

目的:探讨环氧合酶－2抑制剂对大鼠机械通气所致肺损伤的影响.方法:健康成年雄性SD大鼠30只,随机分为3组(n=10):常规潮气量通气组(TV组,潮气量8 mL/kg)、大潮气量通气组(HV组,潮气量40 mL/kg)、大潮气量通气＋环氧合酶-2选择性抑制剂组(HV+NS398组).HV+NS398组于机械通气前30 min腹腔注射NS398 8 mg/kg.于机械通气4h时处死大鼠,Western Blot法检测肺组织中水通道蛋白1(AQP1)表达;检测支气管肺泡灌洗液(BALF)中肿瘤坏死因子(TNF-α)、白介素6(IL-6)、血栓素B2(TXB2)含量及总蛋白浓度,计算肺组织湿/干重比(W/D).结果:与TV组相比,HV组AQP1表达降低(P＜0.05),BALF中TNF-α、IL-6、TXB2和总蛋白浓度增加,肺组织W/D升高(P＜0.05);与HV组相比,HV+NS398组AQP1表达升高,BALF中TNF-α、IL-6、TXB2和总蛋白浓度降低(P＜0.05),肺组织W/D降低(P＜0.05).结论:环氧合酶-2抑制剂可能通过上调AQP1的表达及减轻炎性反应程度,而缓解大鼠机械通气所致肺损伤.

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

AIM: To investigate the effect of cyclooxygenase 2 inhibitor on ventilator-induced lung injury in rats.METHODS: Thirty healthy adult male SD rats weighing 300-350 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);group HV+NS398(pretreated with NS398 8 mg/kg before ventilating).The animals were anesthetized with intraperitoneal 20% urethane 8 mL/kg,tracheotomized,intubated and mechanically ventilated for 4 h.Group HV+NS398 was given with intraperitoneal injection at 30 min before mechanical ventilation.The animals were sacrificed at 4 h after mechanical ventilation.The lungs were removed for determination of bronchoalveolar lavage fluid(BALF) TNF-α,IL-6,TXB2,total protein concentration,wet to dry weight ratio(W/D).Expression of aquaporin 1(AQP1) was analyzed by Western Blot.RESULTS:Expression of AQP1 was decreased significantly in group HV than that in group TV(P<0.05).The BALF concentration of TNF-α,IL-6,TXB2,total protein and W/D were higher in group HV than those in group TV(P<0.05).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 might relate to upregulate expressionof aquaporin 1and lessen inflaming response.