Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
J Pineal Res. 2013 Mar;54(2):207-21. doi: 10.1111/jpi.12020. Epub 2012 Oct 30.
This study investigated whether melatonin-treated adipose-derived mesenchymal stem cells (ADMSC) offered superior protection against acute lung ischemia-reperfusion (IR) injury. Adult male Sprague-Dawley rats (n = 30) were randomized equally into five groups: sham controls, lung IR-saline, lung IR-melatonin, lung IR-melatonin-normal ADMSC, and lung IR-melatonin-apoptotic ADMSC. Arterial oxygen saturation was lowest in lung IR-saline; lower in lung IR-melatonin than sham controls, lung IR-melatonin-normal ADMSC, and lung IR-melatonin-apoptotic ADMSC; lower in lung IR-melatonin-normal ADMSC than sham controls and lung IR-melatonin-apoptotic ADMSC; lower in lung IR-melatonin-apoptotic ADMSC than sham controls (P < 0.0001 in each case). Right ventricular systolic blood pressure (RVSBP) showed a reversed pattern among all groups (all P < 0.0001). Changes in histological scoring of lung parenchymal damage and CD68+ cells showed a similar pattern compared with RVSBP in all groups (all P < 0.001). Changes in inflammatory protein expressions such as VCAM-1, ICAM-1, oxidative stress, TNF-α, NF-κB, PDGF, and angiotensin II receptor, and changes in apoptotic protein expressions of cleaved caspase 3 and PARP, and mitochondrial Bax, displayed identical patterns compared with RVSBP in all groups (all P < 0.001). Numbers of antioxidant (GR+, GPx+, NQO-1+) and endothelial cell biomarkers (CD31+ and vWF+) were lower in sham controls, lung IR-saline, and lung IR-melatonin than lung IR-melatonin-normal ADMSC and lung IR-melatonin-apoptotic ADMSC, and lower in lung IR-melatonin-normal ADMSC than lung IR-melatonin-apoptotic ADMSC (P < 0.001 in each case). In conclusion, when the animals were treated with melatonin, the apoptotic ADMSC were superior to normal ADMSC for protection of lung from acute IR injury.
本研究旨在探讨褪黑素处理的脂肪间充质干细胞（ADMSC）是否能更好地预防急性肺缺血再灌注（IR）损伤。成年雄性 Sprague-Dawley 大鼠（n=30）随机均分为 5 组：假手术对照组、肺 IR-盐水组、肺 IR-褪黑素组、肺 IR-褪黑素-正常 ADMSC 组和肺 IR-褪黑素-凋亡 ADMSC 组。动脉血氧饱和度在肺 IR-盐水组最低；在肺 IR-褪黑素组比假手术对照组、肺 IR-褪黑素-正常 ADMSC 组和肺 IR-褪黑素-凋亡 ADMSC 组更低；在肺 IR-褪黑素-正常 ADMSC 组比假手术对照组和肺 IR-褪黑素-凋亡 ADMSC 组更低；在肺 IR-褪黑素-凋亡 ADMSC 组比假手术对照组更低（每组均 P<0.0001）。各组右心室收缩压（RVSBP）均呈相反模式（均 P<0.0001）。各组肺组织损伤和 CD68+细胞的组织学评分变化与 RVSBP 呈相似模式（均 P<0.001）。炎症蛋白表达的变化，如 VCAM-1、ICAM-1、氧化应激、TNF-α、NF-κB、PDGF 和血管紧张素 II 受体，以及凋亡蛋白表达的变化，如 cleaved caspase 3 和 PARP、线粒体 Bax，在各组中与 RVSBP 呈相同模式（均 P<0.001）。抗氧化剂（GR+、GPx+、NQO-1+）和内皮细胞标志物（CD31+和 vWF+）的数量在假手术对照组、肺 IR-盐水组和肺 IR-褪黑素组比肺 IR-褪黑素-正常 ADMSC 组和肺 IR-褪黑素-凋亡 ADMSC 组更低，在肺 IR-褪黑素-正常 ADMSC 组比肺 IR-褪黑素-凋亡 ADMSC 组更低（每组均 P<0.001）。综上所述，当动物接受褪黑素治疗时，凋亡 ADMSC 比正常 ADMSC 更能保护肺免受急性 IR 损伤。
