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 4 h 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.