目的 研究褪黑素对大鼠肠缺血再灌注肺损伤的保护作用及其对N-myc 下游调节基因2( NDRG2) 表达的影响。
方法 将健康雄性SD 大鼠40 只随机分为褪黑素高剂量组( 10 mg/kg) 、褪黑素低剂量组( 1 mg/kg) 、缺血再灌注组和假手术组。褪黑素高、低剂量组造模前30 min给予腹腔注射褪黑素, 缺血再灌注组和假手术组造模前30 min 腹腔注射与褪黑素治疗量等容量的生理盐水。褪黑素高、低剂量组和缺血再灌注组大鼠经夹闭肠系膜上动脉, 缺血60 min后松开动脉夹造成再灌注, 建立肠缺血再灌注肺损伤模型, 于再灌注45 min 后取右肺组织。假手术组全身麻醉后只切除右肺, 缝合切口。观察肺组织病理学改变和湿/干重比值( W/D) , 免疫组化、Western-blot 方法观察大鼠肺组织NDRG2 的表达。
结果 与假手术组比较, 缺血再灌注组肺泡壁增宽, 肺泡腔内可见出血等炎症表现, W/D 显著升高, 肺组织NDRG2 蛋白表达明显降低。与缺血再灌注组比较, 褪黑素高、低剂量组肺泡腔内出血等炎症表现减轻,W/D显著降低, 肺组织NDRG2 蛋白表达明显增强。褪黑素高、低剂量组间各指标均无显著差异。
结论 褪黑素可能通过上调NDRG2 的表达而减轻肠缺血再灌注造成的肺损伤。
Objective To observe the effects of melatonin on lung injury and NDRG2 ( N-myc downstream-regulated gene 2) expression after intestinal ischemia-reperfusion ( I/R) .
Methods 40 healthy SD rats were randomly assigned to a sham group, an I/R group, a high-dose melatonin group ( 10 mg/kg) , and a low-dose melatonin group ( l mg/kg) . The model of lung injury was established by superior mesenteric artery clamping/unclamping. 30 minutes before clamping, melatonin was administered intraperitoneally to the rats in two melatonin groups, and normal saline in same volume was administered to the rats in the I/R group and the shamgroup. Then superior mesenteric arteries of the rats in the I/R group and two melatonin groups were clamped for 60 minutes. 45 minutes after unclamping, right lung tissues were sampled for pathological examination and wet/dry ( W/D) ratio measurement. The rats in the sham group underwent sham operation without clamping. The expression of NDRG2 protein in the lung tissue was detected by immunohistochemistry and Western-blot.
Results Compared with the sham group, hemorrhage and inflammation of lung tissues were observed. The W/D was obviously increased and the NDRG2 expression was significantly decreased in the I/R group. Compared with the I/R group, mild hemorrhage and inflammation changes of lung tissues were observed and the W/D was decreased while the NDRG2 protein expression was increased significantly in two melatonin groups. There was no significant difference between two melatonin groups.
Conclusion Melatonin may relieve lung injury after intestinal ischemia-reperfusion through up-regulating NDRG2 expression.
引用本文： 杨波,张志培,姜鹏,尚荣鑫,韩国梁,葛鹏,姜涛. 褪黑素对大鼠肠缺血再灌注肺损伤及N-myc 下游调节基因2 表达的影响. 中国呼吸与危重监护杂志, 2013, 12(1): 61-64. doi: 10.7507 /1671 -6205.20130014 复制