Inhaled NO contributes to lung repair in piglets with acute respiratory distress syndrome via increasing circulating endothelial progenitor cells.
Inhaled NO contributes to lung repair in piglets with acute respiratory distress syndrome via increasing circulating endothelial progenitor cells.
复制标题
吸入一氧化氮通过增加循环内皮祖细胞，有助于患有急性呼吸窘迫综合征的仔猪的肺修复。
DOI：
10.1371/journal.pone.0033859
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Sun L
中科院分区：
文献类型：
--
作者：
Qi Y;Qian L;Sun B;Liu L;Wu P;Sun L
一氧化氮 (NO) 在内皮祖细胞 (EPC) 的动员中发挥着重要作用。我们假设吸入一氧化氮 (iNO) 会诱导 EPC 动员，从而促进急性呼吸窘迫综合征 (ARDS) 的肺修复。健康仔猪被随机分为四组 (n = 6)： 对照组（Con；仅机械通气）； ARDS（通过油酸输注和机械通气建立）； ARDS 加粒细胞集落刺激因子（G-CSF；10 µg/kg/d 皮下注射）； ARDS 加 NO 吸入（iNO；10 ppm）。在不同时间点（基线、0、24、72 和 168 小时）测定 EPC 和动员细胞因子，并在 168 小时评估损伤修复。与Con组相比，24小时时ARDS组骨髓中EPCs水平升高，但血液中EPCs水平没有升高。与ARDS组相比，吸入NO引起血液中CD34+KDR+、KDR+CD133+和CD34+KDR+CD133+ EPCs数量快速升高（2163±454 vs. 1094±416、1302±413 vs. 429±244、1140±494 vs. 453±273 cells/ml，分别，P<0.05），并且骨髓中 KDR+CD133+ 细胞的百分比减少。与 ARDS 相比，iNO 组的肺 CD34、CD133、VEGF、VEGF 受体 2、内皮 NO 合酶 mRNA 以及 VEGF 和 VEGF 受体 2 蛋白表达水平升高，但 G-CSF 组则没有升高。此外，与ARDS治疗相比，iNO治疗降低了血管通透性，增加了肺血管密度，并减轻了肺水肿和炎症。 72 小时时，iNO 组的血浆 VEGF、基质细胞衍生因子 1 (SDF-1) 和骨髓 NO2 -/NO3 - 显着高于 ARDS 组。这些结果表明，iNO 诱导 EPC 从骨髓动员到循环中，有助于血管修复，从而减轻肺损伤。
Nitric oxide (NO) plays an important role in mobilization of endothelial progenitor cells (EPCs). We hypothesized that inhaled NO (iNO) would induce EPC mobilization and therefore promote lung repair in acute respiratory distress syndrome (ARDS). Healthy piglets were randomized into four groups (n = 6): Control (Con; mechanical ventilation only); ARDS (established by oleic acid infusion and mechanical ventilation); ARDS plus granulocyte-colony stimulating factor (G-CSF; 10 µg/kg/d subcutaneously); ARDS plus NO inhalation (iNO; 10 ppm). EPCs and mobilizing cytokines were assayed at different time points (baseline, 0, 24, 72 and 168 h) and injury reparation was assessed at 168 h. Compared to the Con group, the levels of EPCs were increased in bone marrow but not in blood in the ARDS group at 24 h. Compared to the ARDS group, inhaled NO induced a rapid elevation in the number of CD34+KDR+, KDR+CD133+ and CD34+KDR+CD133+ EPCs in blood (2163±454 vs. 1094±416, 1302±413 vs. 429±244, 1140±494 vs. 453±273 cells/ml, respectively, P<0.05), and a reduction in the percentage of KDR+CD133+ cells in bone marrow. Lung CD34, CD133, VEGF, VEGF receptor 2, endothelial NO synthase mRNA, and VEGF and VEGF receptor 2 protein expression levels were augmented in the iNO group, but not in the G-CSF group, compared to ARDS. Furthermore, iNO treatment reduced vascular permeability, increased pulmonary vessel density, and alleviated pulmonary edema and inflammation compared to ARDS treatment. Plasma VEGF, stromal cell-derived factor-1 (SDF-1) and bone marrow NO2 −/NO3 − were significantly higher in the iNO group compared to the ARDS group at 72 h. These results suggest that iNO induces mobilization of EPCs from bone marrow into circulation, contributes to vascular repair, and thereby alleviates lung damage.