低温下一氧化碳通气对无心跳大鼠供肺的保护机制研究

Ventilation with cooled carbon monoxide protects non-heart-beating donor rat lungs against worm ischemic injury

目的探讨低温一氧化碳通气对无心跳大鼠供肺的保护机制。方法SD大鼠制成无心跳供鼠，分别行常温空气（对照组）、常温一氧化碳（常温一氧化碳组）和低温一氧化碳（低温一氧化碳组）机械通气，并进行大鼠左肺移植。评估无心跳供肺热缺血期间的温度变化，再灌注后测定动脉血氧分压、测定湿／干移植肺组织质量比值（W／D）、髓过氧化物酶（MPO）活性和支气管肺泡灌洗液（BAL）中性粒细胞计数等，同时检测移植肺组织中白细胞介素1p（IL-1p）和胱天蛋白酶3mDNA的表达量。结果低温一氧化碳组的支气管内和肺表面温度低于对照组及常温一氧化碳组（P〈0．01）。移植肺再灌注后1、2和4h时低温一氧化碳组的动脉血氧分压显著高于对照组和常温一氧化碳组（P〈0．05）。再灌注4h后，低温一氧化碳组的移植肺组织的W／D、MPO活性、BAL中性粒细胞计数值、IL-Iβ和胱天蛋白酶3mRNA的相对表达量均低于对照组和常温一氧化碳组（P〈0．05）。结论低温一氧化碳通气可以加强一氧化碳抑制前炎症因子IL-Iβ和凋亡相关基因胱天蛋白酶3的表达，更好的减轻无心跳供鼠供肺的热缺血损伤。

Objective Lungs from non-heart-beating donors for transplantation require protection against warm ischemic damage. This study investigated the preservative effect of Ventilation with cooled carbon monoxide during warm ischemia in non-heart-beating donor rat lungs. Method 18 rats were divided into a CO group （n = 6）, which received ventilation with low-dose carbon monoxide at normal temperature during a 4-hour warm ischemic period; a Control group （n = 6）, which received no ventilation at normal temperature; a cooling CO group （n = 6）, which received ventilation with cooled carbon monoxide. PaO2, Myeloperoxidase （MPO） activity, Bronchoalveolar lavage （BAL） neutrophil count and the wet-to-dry （W/D） lung weight ratio were recorded in every group. Quantitative real-time RT-PCR was used to analysis the expression of IL-113 and caspase 3 mRNA in graft lung tissures. Result Endobronchial temperatures and lung surface temperatures in the Cooling CO group were lower than those in the corresponding Control group and CO group （P〈 0. 01）. Lower wet/dry lung weight ratio, MPO activity, BAL neutrophil count, expression of IL-1βand caspase 3 mRNA in graft lung fissures were seen in the Cooling group compared with the Control group and CO group （P〈0. 05）. Conelusion Ventilation with cooled carbon monoxise can decrease lung temperature and improve the protecting effect on non-heart-beating donor rat lungs againt worm ischemic injury by inhibiting the expression of proimflammatory factor Ib-1β and apoptosis-associated gene caspase 3.