脑死亡供体鼠吸入一氧化碳对受体鼠移植肺损伤的影响

目的 评价脑死亡供体鼠吸入一氧化碳(CO)对受体鼠移植肺损伤的影响.方法 雄性Wistar大鼠24只,体重250～300 g,随机分为3组(n=8),接受非脑死亡供体肺组(NBD组)供体鼠颅内置入Fogarty导管,但不诱导脑死亡,观察2.5 h;接受吸入氧气的脑死亡供体肺组(BDO2组)供体鼠确认脑死亡后吸入40%氧气2 h;接受吸入CO的脑死亡供体肺组(BDCO组)供体鼠确认脑死亡后吸入40%氧气和0.025%CO混合气2 h.处理结束后取供体左肺,进行原位异体肺移植,受体鼠每30 min进行一次动脉血气分析.肺移植成功后2 h处死受体鼠,采集右股动脉血样,采用嘌呤氧化酶法测定血浆超氧化物歧化酶(SOD)活性;采用硫代巴比妥酸法测定丙二醛(MDA)浓度;采用ELISA法测定血浆白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α和IL-10浓度.计算移植肺组织湿/干重比(W/D);测定移植肺组织髓过氧化物酶(MPO)活性,并进行移植肺组织损伤评分.结果 与C组比较,BDO2组和BDCO组PaO2/FiO2、BE、pH值和血浆SOD活性、IL-10浓度降低,移植肺组织W/D、MPO活性、损伤评分和血浆MDA、IL-6、TNF-α浓度升高(P<0.05);与BD02组比较,BDCO组PaO2/FiO2、BE、pH值和血浆SOD活性、IL-10浓度升高,移植肺组织W/D、MPO活性、损伤评分和血浆MDA、IL-6、TNF-α浓度降低(P<0.05).结论 脑死亡供体鼠吸入CO 2 h可减轻受体鼠移植肺损伤,其机制可能是吸入CO提高了移植肺的抗氧化能力,减轻了移植后局部和全身炎性反应.

Effects of carbon monoxide inhalation by brain death donor on the transplanted lung Injury in recipient of rats

Objective To investigate the effects of carbon monoxide (CO) inhalation by brain death (BD) donor on transplanted lung injury in recipient of rats. Methods Twenty-four male Wistar rats weighing 250-300 g were randomly divided into 3 groups ( n = 8 each) : group Ⅰ donor without brain death (NBD) ; group Ⅱ brain death donor inhaling O2 (BDO2) and group Ⅲ brain death donor inhaling CO (BDCO). The donor rats were anesthetized with intraperitoneal pentobarbital sodium 60 mg/kg, trachoostomized and mechanically ventilated (VT 10 ml/kg, RR 50 bpm, PEEP 2 cm H2O). BD was induced by inserting a Fogarty catheter into the skull and brain was compressed by inflating the balloon according to Avlonitis VS. After BD was confirmed, 40% O2 was inhaled for 2 h in group Ⅱ and a mixture of 40% O2 + 0.025% CO was inhaled for 2 h in group Ⅲ . MAP was maintained at 80-100 mm Hg. Cuff technique was used for orthotopic left lung transplantation according to Mizobuchi T.Arterial blood samples were obtained every 30 min in recipient for blood gas analysis. The recipients were killed by exsangmnation at 2 h after lung transplantation and blood was collected for determination of SOD activity and MDA, IL-6, IL-10 and TNF-α concentrations. The transplant lung was removed for determination of W/D lung weight ratio, MPO activity in the lung tissue and microscopic examination. Lung injury scores were calculated. Results PaO2/FiO2, BE, pH, plasma SOD activity and IL-10 concentrations were significantly lower while W/D lung weight ratio, MPO activity in the lung tissue and lung injury scores of the transplant lung were significantly higher in group BDO2 and BDCO than in group (NBD). PaO2/FiO2, BE, pH, plasma SOD activity and IL-10 concentration were significantly higher and W/D ratio, MPO activity in the lung tissue, lung injury scores of the transplant lung and plasma concentrations of MDA, IL-6 and TNF-α were significantly lower in group BDCO than in group BDO2. Conclusion Inhalation of CO for 2 h by BD transplant donor can attenuate the donor lung injury after transplantation in recipient by suppression of local and systemic inflammatory response and enhancing anti-oxidant activity.