胆绿素对脑死亡致大鼠肺损伤的影响

Effects of biliverdin on lung injury induced by brain death in rats

目的 评价胆绿素对脑死亡致大鼠肺损伤的影响.方法 成年雄性清洁级Wistar大鼠23只,体重250～300 g,随机分为3组,假手术组（S组,n=7）仅向大鼠颅内置入Fogarty导管;脑死亡组（BD组,n=8）和胆绿素组（B组,n=8）向大鼠颅内置入Fogarty导管,通过膨胀球囊诱导脑死亡,膨胀球囊后30 min确认脑死亡情况,发生脑死亡后分别腹腔注射生理盐水1 ml或胆绿素35 mg/kg.分别于给予胆绿素前、后间断采集动脉血样,进行血气分析,计算PaO2/FiO2,并测定血浆胆红素浓度.给予胆绿素后1.5 h处死大鼠,取肺组织,测定MDA含量、SOD活性、总抗氧化能力、肺组织细胞凋亡情况及胆绿素还原酶的表达水平,对细胞凋亡情况进行免疫组化评分.结果 与S组比较,BD组PaO2/FiO2、SOD活性和总抗氧化能力降低,MDA含量和凋亡细胞免疫组化评分升高（P＜0.05）;与BD组比较,B组PaO2/FiO2、胆红素浓度、SOD活性、总抗氧化能力和胆绿素还原酶表达水平升高,MDA含量和凋亡细胞免疫组化评分降低（P＜0.05）.结论 外源性给予胆绿素可减轻脑死亡致大鼠肺损伤,其机制与抑制肺组织氧化应激反应和细胞凋亡有关.

Objective To investigate the effects of exogenous biliverdin on lung injury induced by brain death （BD） in rats. Methods Twenty-three adult male Wistar rats in which Fogarty balloon catheter was successfully inserted into cranial cavity were randomly divided into 3 groups： group Ⅰ sham operation （group S,n = 7）; group Ⅱ brain death （group BD, n = 8） and group Ⅲ biliverdin ＋ BD （group B, n = 8）. The animals were anesthetized, intubated and mechanically ventilated. Femoral artery and vein were cannulated for MAP monitoring and drug and fluid administration. Brain death was induced by injecting slowly normal saline into the balloon in group Ⅱ and Ⅲ. BD was confirmed by dilated and fixed pupils, apnea, transient hypertension and EEG changes. In group Ⅲ biliverdin 35 mg/kg was injected intraperitoneally as soon as BD was confirmed. The animals were mechanically ventilated for another 1.5 h during which MAP was maintained at 80-120 mm Hg by iv norepinephrine infusion. Arterial blood samples were obtained before anesthesia, immediately before and at 5, 30,60, 90 min after intraperitoneal biliverdin for blood gas analysis and determination of plasma bilirubin concentration. PaO2/FiO2 was calculated. The animals were sacrificed at 1.5 h after biliverdin administration. The left lung was removed for detection of MDA content, SOD activity, total antioxidant capacity, cell apoptosis and biliverdin reductase expression in lung tissue. Results Brain death significantly decreased PaO2/FiO2, lung SOD activity and total antioxidant capacity and increased lung MDA content and apoptosis as compared with sham operation group. IP biliverdin significantly attenuated BD-induced lung injury in group B as compared with group BD. The plasma bilirubin concentration and biliverdin reductase expression were significantly higher in group B than group BD. Conclusion Exogenous biliverdin can attenuate BD-induced lung injury by inhibiting pulmonary oxidative stress response and apoptosis.