脂肪来源间充质干细胞自体移植显著减轻了啮齿动物模型的急性缺血再灌注肺损伤。

BACKGROUND

This study tested the hypothesis that autologous transplantation of adipose-derived mesenchymal stem cells (ADMSCs) can effectively attenuate acute pulmonary ischemia-reperfusion (IR) injury.

METHODS

Adult male Sprague-Dawley (SD) rats (n = 24) were equally randomized into group 1 (sham control), group 2 (IR plus culture medium only), and group 3 (IR plus intravenous transplantation of 1.5 × 106 autologous ADMSCs at 1h, 6h, and 24h following IR injury). The duration of ischemia was 30 minutes, followed by 72 hours of reperfusion prior to sacrificing the animals. Blood samples were collected and lungs were harvested for analysis.

RESULTS

Blood gas analysis showed that oxygen saturation (%) was remarkably lower, whereas right ventricular systolic pressure was notably higher in group 2 than in group 3 (all p < 0.03). Histological scoring of lung parenchymal damage was notably higher in group 2 than in group 3 (all p < 0.001). Real time-PCR demonstrated remarkably higher expressions of oxidative stress, as well as inflammatory and apoptotic biomarkers in group 2 compared with group 3 (all p < 0.005). Western blot showed that vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, oxidative stress, tumor necrosis factor-α and nuclear factor-κB were remarkably higher, whereas NAD(P)H quinone oxidoreductase 1 and heme oxygenase-1 activities were lower in group 2 compared to those in group 3 (all p < 0.004). Immunofluorescent staining demonstrated notably higher number of CD68+ cells, but significantly fewer CD31+ and vWF+ cells in group 2 than in group 3.

CONCLUSION

ADMSC therapy minimized lung damage after IR injury in a rodent model through suppressing oxidative stress and inflammatory reaction.

背景

本研究旨在验证脂肪间充质干细胞（ADMSC）自体移植可有效减轻急性肺缺血再灌注（IR）损伤这一假说。

方法

成年雄性 Sprague-Dawley（SD）大鼠（n = 24）等分为三组：1 组（假手术对照）、2 组（IR 后仅给予培养基）和 3 组（IR 后 1h、6h 和 24h 分别经静脉内移植 1.5×106 个自体 ADMSC）。缺血 30 分钟，再灌注 72 小时后处死动物。采集血样并取肺组织进行分析。

结果

血气分析显示，与 3 组相比，2 组氧饱和度（%）明显更低，右心室收缩压明显更高（均 p < 0.03）。2 组肺组织损伤的组织学评分明显高于 3 组（均 p < 0.001）。实时 PCR 显示，与 3 组相比，2 组氧化应激、炎症和凋亡生物标志物的表达明显更高（均 p < 0.005）。Western blot 显示，与 3 组相比，2 组血管细胞黏附分子（VCAM）-1、细胞间黏附分子（ICAM）-1、氧化应激、肿瘤坏死因子-α和核因子-κB 明显更高，而 NAD（P）H 醌氧化还原酶 1 和血红素加氧酶-1 活性明显更低（均 p < 0.004）。免疫荧光染色显示，与 3 组相比，2 组 CD68+细胞明显更多，CD31+和 vWF+细胞明显更少。