Melatonin augments apoptotic adipose-derived mesenchymal stem cell treatment against sepsis-induced acute lung injury.
Melatonin augments apoptotic adipose-derived mesenchymal stem cell treatment against sepsis-induced acute lung injury.
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发表时间：
2014-10
影响因子：
2.2
通讯作者：
Hong-Hwa Chen;Chia‐Lo Chang;Kun‐Chen Lin;P. Sung;Han‐Tan Chai;Yen-yi Zhen;Yi-ching Chen;Ying-Chung Wu;S. Leu;Tzu-hsien Tsai;Chih-hung Chen;Hsueh-Wen Chang;H. Yip
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作者：
Hong-Hwa Chen;Chia‐Lo Chang;Kun‐Chen Lin;P. Sung;Han‐Tan Chai;Yen-yi Zhen;Yi-ching Chen;Ying-Chung Wu;S. Leu;Tzu-hsien Tsai;Chih-hung Chen;Hsueh-Wen Chang;H. Yip
本研究探讨了褪黑素和凋亡脂肪间充质干细胞（A-ADMSC）联合治疗在改善脓毒症诱导的急性肺损伤方面是否上级ADMSC单独治疗。将成年雄性Sprague-Dawley大鼠（n=50）等比例地随机分成五组：假手术对照组（SC）、盲肠结扎和穿孔（CLP）诱导的脓毒症组、CLP-褪黑激素组、CLP-A-ADMSC组和CLP-褪黑激素-A-ADMSC组。在6、18和72小时，循环白细胞介素（IL）-6在CLP中最高，在SC组中最低，CLP-褪黑激素高于CLP-A-ADMSC和CLP-褪黑激素-A-ADMSC组，CLP-A-ADMSC高于CLP-褪黑激素-A-ADMSC组（所有p<0.001）。72小时的免疫反应性（由循环细胞毒性T细胞和调节性T细胞指示）和WBC计数表现出与循环IL-6相同的模式（所有p<0.001）。肺实质的组织学评分以及CD 68+和CD 14+细胞数量的变化与所有组中IL-6水平的变化相比显示出相似的模式（均p<0.001）。在所有组中，与循环IL-6相比，炎症（氧化应激、RANTES、TNF-α、NF-κB、MMP-9、MIP-1、IL-1β）、凋亡（切割的半胱天冬酶3和PARP、线粒体Bax）、纤维化（Smad 3、TGF-β）标记物和活性氧（NOX-1、NOX-2）的蛋白表达变化显示出相同的模式（所有p<0.001）。抗氧化能力（GR+、GPx+、HO-1、NQO-1+）和血管生成标志物（CXCR 4+细胞）在SC组中最低，但在CLP-褪黑激素-A-ADMSC组中最高，在CLP中低于CLP-褪黑激素和CLP-A-ADMSC组，并且在CLP-褪黑激素中低于CLP-A-ADMSC组（所有p<0.001）。总之，在保护肺免受脓毒症诱导的损伤方面，褪黑激素和A-ADMSC的组合优于单独的A-ADMSC上级。
This study investigated whether combining melatonin and apoptotic adipose-derived mesenchymal stem cells (A-ADMSC) was superior to ADMSC alone in ameliorating sepsis-induced acute lung injury. Adult male Sprague-Dawley rats (n=50) were randomized equally into five groups: sham controls (SC), sepsis induced by cecal-ligation and puncture (CLP), CLP-melatonin, CLP-A-ADMSC, and CLP-melatonin-A-ADMSC. Circulating interleukin (IL)-6 at 6, 18, and 72 hrs, were highest in CLP and lowest in SC groups, higher in CLP-melatonin than CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups, higher in CLP-A-ADMSC than CLP-melatonin-A-ADMSC groups (all p<0.001). Immune reactivity (indicated by circulating cytotoxic-, and regulatory-T cells) and WBC count at 72 h exhibited the same pattern as that of circulating IL-6 (all p<0.001). Changes in histological scoring of lung parenchyma and the number of CD68+ and CD14+ cells showed a similar pattern compared to that of IL-6 level in all groups (all p<0.001). Changes in protein expressions of inflammatory (oxidative stress, RANTES, TNF-α, NF-κB, MMP-9, MIP-1, IL-1β), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), fibrotic (Smad3, TGF-β) markers and those of reactive-oxygen-species (NOX-1, NOX-2) displayed an identical pattern compared to that of circulating IL-6 in all groups (all p<0.001). Anti-oxidative capacities (GR+, GPx+, HO-1, NQO-1+) and angiogenesis marker (CXCR4+ cells) were lowest in SC group but highest in CLP-melatonin-A-ADMSC group, lower in CLP than CLP-melatonin and CLP-A-ADMSC groups, and lower in CLP-melatonin than CLP-A-ADMSC groups (all p<0.001). In conclusion, combined melatonin and A-ADMSC were superior to A-ADMSC alone in protecting the lung from sepsis-induced injury.