Chen Chih-Hung, Chen Yung-Lung, Sung Pei-Hsun, Sun Cheuk-Kwan, Chen Kuan-Hung, Chen Yi-Ling, Huang Tien-Hung, Lu Hung-I, Lee Fan-Yen, Sheu Jiunn-Jye, Chung Sheng-Ying, Lee Mel S, Yip Hon-Kan
Divisions of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Oncotarget. 2017 Jul 17;8(47):82415-82429. doi: 10.18632/oncotarget.19312. eCollection 2017 Oct 10.
This study assessed whether combining adipose-derived mesenchymal stem cells (ADMSC) with preactivated, disaggregated shape-changed platelets (PreD-SCP) was superior to either therapy alone for protecting rat lung from acute respiratory distress syndrome (ARDS) complicated by sepsis. ARDS and sepsis were induced through 100% oxygen inhalation and peritoneal administration of 1.5 mg/kg lipopolysaccharide (LPS), respectively. Adult-male Sprague-Dawley rats (n=40) were randomized into sham-control (SC), ARDS-LPS, ARDS-LPS-ADMSC (1.2x10 cells), ARDS-LPS-PreD-SCP (3.0x10, intravenous administration), and ARDS-LPS-ADMS/PreD-SCP groups, and were sacrificed 72 h after 48 h ARDS induction. Lung injury scores (LIS) and collagen deposition were highest in ARDS-LPS, lowest in SC, higher in ARDS-LPS+ADMSC than in ARDS-LPS+PreD-SCP and ARDS-LPS+ADMS/PreD-SCP, and higher in ARDS-LPS+PreD-SCP than in ARDS-LPS+ADMS/PreD-SCP (all p<0.0001). Alveolar-sac numbers, oxygen saturation, endothelial marker levels, and mitochondrial cytochrome-C levels exhibited opposite patterns with respect to LIS (all p<0.001). Levels of inflammatory, oxidative-stress, apoptosis, mitochondrial/DNA damage, and MAPK and Akt signaling markers exhibited patterns identical to that of LIS (all p<0.001). Anti-oxidant and anti-inflammatory protein levels increased progressively from SC to ARDS-LPS+ADMS/PreD-SCP (all p<0.0001). These findings indicate combined ADMSC/PreD-SCP was superior to either therapy alone for protecting rat lung from ARDS-sepsis injury.
本研究评估了将脂肪来源的间充质干细胞（ADMSC）与预激活、解离且形状改变的血小板（PreD-SCP）联合使用，在保护大鼠肺免受脓毒症并发的急性呼吸窘迫综合征（ARDS）方面是否优于单独使用任何一种治疗方法。分别通过吸入100%氧气和腹腔注射1.5mg/kg脂多糖（LPS）诱导ARDS和脓毒症。成年雄性Sprague-Dawley大鼠（n = 40）被随机分为假手术对照组（SC）、ARDS-LPS组、ARDS-LPS-ADMSC组（1.2×10⁶个细胞）、ARDS-LPS-PreD-SCP组（3.0×10⁶个，静脉注射）和ARDS-LPS-ADMS/PreD-SCP组，并在诱导ARDS 48小时后72小时处死。肺损伤评分（LIS）和胶原沉积在ARDS-LPS组中最高，在SC组中最低，在ARDS-LPS + ADMSC组中高于ARDS-LPS + PreD-SCP组和ARDS-LPS + ADMS/PreD-SCP组，且在ARDS-LPS + PreD-SCP组中高于ARDS-LPS + ADMS/PreD-SCP组（所有p<0.0001）。肺泡囊数量、氧饱和度、内皮标志物水平和线粒体细胞色素C水平与LIS呈现相反的模式（所有p<0.001）。炎症、氧化应激、细胞凋亡、线粒体/DNA损伤以及MAPK和Akt信号标志物的水平呈现与LIS相同的模式（所有p<0.00
