Department of Emergency Medicine, E-Da Hospital, I-Shou University Kaohsiung, Taiwan.
Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan.
Am J Transl Res. 2015 Feb 15;7(2):209-31. eCollection 2015.
This study hypothesized that combined serum-deprived (Sd) and healthy (He) adipose-derived mesenchymal stem cell (ADMSC) therapy is superior to either alone in reducing acute lung ischemia-reperfusion injury (ALIRI).
Adult male Sprague-Dawley (SD) rats (n = 30) were equally randomized into group 1 (sham control), group 2 (ALIRI + culture medium), group 3 (ALIRI + intravenous autologous 1.2 × 10(6) He-ADMSCs at 30 minute, 6 h, and 24 h following lung ischemia/reperfusion for 45 minutes/72 hours, respectively), group 4 (ALIRI + 1.2 × 10(6) Sd-ADMSCs at identical time points after ischemia/reperfusion), and group 5 (ALIRI + 1.2 × 10(6) combined Sd-ADMSC/He-ADMSC 1:1).
Blood oxygen saturation (%) was lowest in group 2, lower in groups 3 to 5 than in group 1, and lower in group 5 than in group 1, whereas right ventricular systolic pressure (RVSP) showed a reverse pattern among the five groups (all p < 0.001). Additionally, changes in histological scoring of lung parenchymal damage, inflammatory and apoptotic biomarkers showed identical pattern compared to that of RVSP in all groups (all p < 0.001). Protein expressions of VCAM-1, ICAM-1, oxidative stress, TNF-α, nuclear factor-κB, and number of CD68 + cells were highest in group 2, higher in groups 3 to 5 than in group 1, and higher in groups 3 and 4 than in group 5, whereas NQO-1 and HO-1 activities and number of CD31 + and vWF + cells showed opposite changes compared with those of inflammatory biomarkers (all p < 0.001).
Combined Sd-ADMSC/He-ADMSC therapy offered superior benefit to either option alone in minimizing rodent ALIRI through suppressing oxidative stress and inflammatory reaction.
本研究假设联合血清剥夺(Sd)和健康(He)脂肪间充质干细胞(ADMSC)治疗优于单独使用任何一种方法,可减少急性肺缺血再灌注损伤(ALIRI)。
成年雄性 Sprague-Dawley(SD)大鼠(n=30)等分为 5 组:1 组(假手术对照)、2 组(ALIRI+培养基)、3 组(ALIRI+静脉内自体 1.2×10(6)He-ADMSCs,分别于肺缺血/再灌注后 30 分钟、6 小时和 24 小时,共 45 分钟/72 小时)、4 组(ALIRI+1.2×10(6)Sd-ADMSCs,于缺血/再灌注后相同时间点)和 5 组(ALIRI+1.2×10(6)联合 Sd-ADMSC/He-ADMSC 1:1)。
第 2 组的血氧饱和度(%)最低,第 3 组至第 5 组的血氧饱和度低于第 1 组,第 5 组的血氧饱和度低于第 1 组,而右心室收缩压(RVSP)在 5 组中呈现相反的模式(均 p<0.001)。此外,肺组织损伤、炎症和凋亡生物标志物的组织学评分变化与 RVSP 在所有组中的变化模式相同(均 p<0.001)。VCAM-1、ICAM-1、氧化应激、TNF-α、核因子-κB 和 CD68+细胞的蛋白表达在第 2 组最高,第 3 组至第 5 组高于第 1 组,第 3 组和第 4 组高于第 5 组,而 NQO-1 和 HO-1 活性和 CD31+和 vWF+细胞的数量与炎症生物标志物的变化相反(均 p<0.001)。
联合 Sd-ADMSC/He-ADMSC 治疗通过抑制氧化应激和炎症反应,提供优于单独使用任何一种方法的益处,可最大限度地减少啮齿动物的 ALIRI。