Autologous Transplantation of Peripheral Blood-derived Circulating Endothelial Progenitor Cells Attenuates Endotoxin-induced Acute Lung Injury in Rabbits by Direct Endothelial Repair and Indirect Immunomodulation
Autologous Transplantation of Peripheral Blood-derived Circulating Endothelial Progenitor Cells Attenuates Endotoxin-induced Acute Lung Injury in Rabbits by Direct Endothelial Repair and Indirect Immunomodulation
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DOI：
10.1097/aln.0b013e3182567f84
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发表时间：
2012-06-01
期刊：
影响因子：
8.8
通讯作者：
Shi, Xue-Yin
中科院分区：
文献类型：
--
作者：
Cao, Jian-Ping;He, Xing-Ying;Shi, Xue-Yin
背景：研究证明循环内皮祖细胞（EPC）在维持正常内皮功能和内皮修复中的作用。本研究旨在观察循环EPCs自体移植对内毒素所致家兔急性肺损伤的保护作用并探讨其机制。方法：纳入家兔150只。内毒素诱导急性肺损伤后，分别静脉输注自体循环EPC、内皮细胞或生理盐水。检查 PaO2/FiO(2) 比率、血浆一氧化氮、丙二醛浓度和超氧化物歧化酶活性。计算肺湿重与干重的比率；测量多形核细胞比率以及透明膜形成和出血的面积。分析IL-1β、E-选择素、细胞间粘附分子-1、IL-10、血管内皮生长因子蛋白和诱导型一氧化氮合酶蛋白的水平。结果：EPC输注后PaO2/FiO(2)比值显着升高。 EPC移植后，多形核细胞浸润、肺湿干重比、肺组织透明膜面积和出血均显着减少。 EPC处理的动物血浆中一氧化氮和丙二醛水平显着受到抑制，超氧化物歧化酶活性增强。 EPC移植显着增加损伤肺组织中白细胞介素10和血管内皮生长因子蛋白的水平，降低白细胞介素1β、E-选择素、细胞间粘附分子1和诱导型一氧化氮合酶的水平。结论：循环EPCs的自体移植可以部分恢复肺内皮功能，通过直接内皮修复和抗氧化和间接免疫调节，有效减轻内毒素引起的急性肺损伤。抗炎。
Background: Studies have demonstrated the role of circulating endothelial progenitor cells (EPCs) in maintaining normal endothelial function and in endothelial repairing. This study was aimed to observe the protective effects of autologous transplantation of circulating EPCs against endotoxin- induced acute lung injury in rabbits and to investigate the underlying mechanisms.Methods: One-hundred-and-fifty rabbits were enrolled. After acute lung injury was induced by endotoxin, autologous circulating EPCs, endothelial cell, or normal saline were transfused intravenously, respectively. PaO2/FiO(2) ratios, concentrations of plasma nitric oxide, malonyldialdehyde, and activity of superoxide dismutase were examined. The lung wet-to-dry weight ratios were counted; polymorphonuclear cell ratios and areas of hyaline membrane formation and hemorrhage were measured. The levels of interleukin-1 beta, E-selectin, intercellular adhesion molecule-1, interleukin-10, vascular endothelial growth factor protein, and inducible nitric oxide synthase protein were analyzed.Results: PaO2/FiO(2) ratios were significantly increased with EPC transfusion. Infiltration of polymorphonuclear cells, lung wet-to-dry weight ratios, and area of hyaline membrane and hemorrhage in lung tissue were significantly decreased after EPC transplantation. Plasma level of nitric oxide and malondialdehyde were significantly inhibited, and the activity of superoxide dismutase was enhanced in the EPC-treated animals. EPC transplantation significantly increased level of interleukin-10 and vascular endothelial growth factor protein and reduced levels of interleukin-1 beta, E-selectin, intercellular adhesion molecule-1, and inducible nitric oxide synthase in injury lung tissues.Conclusions: Autologous transplantation of circulating EPCs can partly restore the pulmonary endothelial function and effectively attenuate endotoxin-induced acute lung injury by direct endothelial repair and indirect immunomodulation of antioxidation and antiinflammation.