环氧合酶-2抑制剂对大鼠机械通气所致肺损伤的影响

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

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8mL/kg)、大潮气量通气组(HV组,潮气量40mL/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30min腹腔注射NS398 8mg/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。

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 ani- mals 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 an- imals were sacrificed at 4 h after mechanical ven- tilation. The lungs were removed for determina- tion of bronchoalveolar lavage fluid （BALF） TNF-α, IL-6, TXB2, total protein concentration, wet to dry weight ratio （W/D）. Expres- sion 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 con- centration 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 inhibi- tor significantly attenuated the HV-indueed changes listed above in group HV-F NS398. CONCLUSION： Cyclooxygenase 2 inhibitor at- tenuates ventilation-induced lung injury in rats. Its mechanism might relate to upregulate expres- sionof aquaporin land lessen inflaming response.