内皮素-1受体拮抗剂对兔单侧肺通气时肺损伤的保护作用

Protective effects of endothelin-1 recepter antagonist against lung injury during one-lung ventilation in rabbits

目的观察内皮素-1(ET-1)受体拮抗剂对兔单侧肺通气(OLV)时肺损伤的保护作用.方法日本大耳白兔15只,雌雄不分,随机分为3组(n=5):对照组(T组)、OLV组(O组)、OLV± BQ-123组(OB组).T组持续双肺通气2.5h,O组及OB组先行右侧单肺通气2.0h,之后恢复双肺通气0.5h.OB组在单侧肺通气前10 min经股静脉注射ET-1受体拮抗剂(BQ-123) 50 μg/kg,O组及OB组同一时间点注射同等量的生理盐水.取OLV前(T0)、OLV 1 h(T1)、OLV 2 h(T2)及双肺通气0.5 h(T3)4个时间点抽动脉血,计算氧合指数(OI);取兔肺组织行病理学检查并计算肺损伤评分;取兔肺组织制备匀浆测ET-1含量、超氧化物酶(SOD)活性、肺肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)浓度.应用SPSS 20.0统计软件分析,计量资料采用均值±标准差(Mean±SD)表示,组间数据比较采用重复测量单因素方差分析,组内左右肺比较采用配对t检验.结果与T组比较,O组萎陷侧肺组织中ET-1含量[(165.73±23.87) ng/L比(94.31±9.86)ng/L]升高、SOD活性[(62.21±2.10) U/mg比(84.42±6.77)U/mg]降低,IL-6含量[(20.82±1.33) ng/L比(7.97±1.98) ng/L]及TNF-α浓度[(37.11 ±5.03) ng/L比(19.47±4.30) ng/L]升高(P<0.05),病理评分升高,单肺通气2.0h时OI降低.与O组比较,OB组萎陷侧肺组织中ET-1含量[(119.37±8.55) ng/L比(165.73±23.87) ng/L)降低、SOD活性[(78.29±1.78) U/mg比(62.21 ±2.10) U/mg]增高,IL-6含量[(14.13±1.26) ng/L比(20.82±1.33) ng/L]及TNF-α含量[(26.30±2.18) ng/L比(37.11±5.03) ng/L]降低(P<0.05),病理评分降低,单肺通气2.0h时OI升高.在O组及OB组中,与通气侧肺比较,萎陷侧肺组织中ET-1、IL-6及TNF-α含量明显增高,SOD活性降低,病理评分增加(P<0.05).结论 ET-1受体拮抗剂对兔单侧肺通气时肺损伤有保护作用,可能与减少肺组织中ET-1与受体结合及抑制肺组织的炎性反应和氧化应激反应有关.

Objective To investigate the protective effect of endothelin-1 (ET-1) recepter antagonist against lung injury during one-lung ventilation (OLV) in rabbits. MethodsFifteen big-ear Japanese rabbits (no limit of male or female) were divided into 3 groups randomly (n=5 in each group): sham group (group T), one-lung ventilation group (group O), OLV+ BQ-123 group (group OB). Two lungs were ventilated for 2.5 h in group T, and one lung was ventilated for 2.0 h followed by 0.5 h OLV in group O and group OB. About 10 min before one lung ventilation, BQ-123 (50 μg/kg) was injected through the femoral vein in group OB. Group O and group OB received the same amount of normal saline at the same time point. During the experiment, arterial blood gas analyses were done at the time of before OLV (T0), 1 h after OLV (T1), 2 h after OLV (T2) and 0.5 h after TLV (T3), as well as OI was calculated. At end of the experiment, the two lungs were removed for light microscopic evaluations, and the content of ET-1, activity of superoxide dismutase (SOD), concentrations of tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) were determined in lung tissures. ResultsAs compared with group T, the content of ET-1 [(165.73±23.87) ng/L vs.(94.31±9.86) ng/L], the activity of SOD [(62.21±2.10) U/mg vs.(84.42±6.77) U/mg], the concentration of IL-6 [(20.82±1.33) ng/L vs.(7.97±1.98) ng/L] and TNF-α[(37.11±5.03) ng/L vs.(19.47±4.30) ng/L](P<0.05) in lung tissue of group O were increased, the pathological score was increased, and the OI was decreased at 2.0 hafter one-lung ventilation. As compared with group O, the content of ET-1 [(119.37±8.55) ng/L vs.(165.73±23.87) ng/L], the activity of SOD [(78.29±1.78) U/mg vs.(62.21±2.10) U/mg] and the concentrations of IL-6 [(14.13±1.26) ng/L vs.(20.82±1.33) ng/L] and TNF-α[(26.30±2.18) ng/L vs.(37.11±5.03) ng/L] in the collapsed lung tissue of group OB were decreased (P<0.05), and the pathological score decreased. In group O and OB, the content of ET-1 and concentrations of IL-6 and TNF-α in the collapsed lung were significantly higher than those in the ventilated lung, the activity of SOD was decreased and the pathological score was increased (P<0.05). ConclusionET-1 receptor antagonist has protective effect on lung injury during one-lung ventilation in rabbits, which may be related to the reduction of ET-1 binding to receptor and the inhibition of inflammatory response and oxidative stress reaction in lung tissue.