Department of Intensive Care Unit, The Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
Arch Med Res. 2018 Apr;49(3):172-181. doi: 10.1016/j.arcmed.2018.08.006. Epub 2018 Aug 14.
Mechanical ventilation (MV) can cause ventilator-induced lung injury (VILI).
This study investigated whether endothelial colony-forming cells (ECFC) could inhibit VILI in a rat model of acute respiratory distress syndrome (ARDS).
Male Wistar rats received the femoral artery and venous cannulation (sham group) or were injected intravenously with 500 μg/kg lipopolysaccharide to induce ARDS. The ARDS rats were subjected to MV. Immediately after the MV, the rats were randomized and injected intravenously with vehicle (ARDS group) or ECFC (ECFC group, n = 8 per group). The oxygen index, lung wet-to-dry weight (W/D) ratios, cytokine protein levels in serum or bronchoalveolar lavage fluid (BALF), neutrophil counts, neutrophil elastase and total protein levels in BALF, histology and cell apoptosis in the lung were detected. The protein levels of endothelin-1, inducible nitric oxide synthase (iNOS), endothelial NOS, matrix metalloproteinase (MMP)-9, Bax, Bcl-2, gelsolin, cleaved caspase-3, phosphorylated NF-κBp65 and myosin light chain (MLC) in the lung were analyzed.
Compared with the ARDS group, treatment with ECFC significantly increased the oxygen index, and decreased the lung W/D ratios and injury, and the numbers of apoptotic cells in the lungs, neutrophils counts, total protein and elastase concentrations in BALF of rats. ECFC treatment significantly minimized the protein levels of pro-inflammatory cytokines in BALF and serum, but increased interleukin 10 in rats. Furthermore, ECFC treatment significantly reduced the protein levels of endothelin-1, iNOS, Bax, Gelsolin, MMP-9, cleaved caspase-3, phosphorylated NF-κBp65 and MLC, but enhanced eNOS and Bcl-2 in the lungs of rats.
Therefore, ECFC attenuated inflammation, cell apoptosis and VILI in ARDS rats.
机械通气（MV）可导致呼吸机相关性肺损伤（VILI）。
本研究旨在探讨内皮祖细胞（ECFC）能否抑制急性呼吸窘迫综合征（ARDS）大鼠模型中的 VILI。
雄性 Wistar 大鼠接受股动静脉置管（假手术组）或静脉注射 500μg/kg 脂多糖诱导 ARDS。ARDS 大鼠接受 MV。MV 后立即随机静脉注射载体（ARDS 组）或 ECFC（ECFC 组，每组 8 只）。检测氧指数、肺湿重/干重（W/D）比值、血清或支气管肺泡灌洗液（BALF）中细胞因子蛋白水平、中性粒细胞计数、BALF 中性粒细胞弹性蛋白酶和总蛋白水平、肺组织学和细胞凋亡。分析肺组织中内皮素-1、诱导型一氧化氮合酶（iNOS）、内皮型一氧化氮合酶、基质金属蛋白酶（MMP）-9、Bax、Bcl-2、凝胶蛋白、裂解 caspase-3、磷酸化 NF-κBp65 和肌球蛋白轻链（MLC）的蛋白水平。
与 ARDS 组相比，ECFC 治疗显著增加了氧指数，降低了肺 W/D 比值和损伤，减少了肺组织中细胞凋亡数量、中性粒细胞计数、BALF 总蛋白和弹性酶浓度。ECFC 治疗明显降低了 BALF 和血清中促炎细胞因子的蛋白水平，但增加了大鼠的白细胞介素 10。此外，ECFC 治疗显著降低了肺组织中内皮素-1、iNOS、Bax、Gelsolin、MMP-9、裂解 caspase-3、磷酸化 NF-κBp65 和 MLC 的蛋白水平，但增强了 eNOS 和 Bcl-2 的表达。
因此，ECFC 减轻了 ARDS 大鼠的炎症、细胞凋亡和 VILI。
