Lin Qing-Ming, Tang Xia-Hong, Lin Shi-Rong, Chen Ben-Dun, Chen Feng
Institute of Fujian Emergency Medicine, Clinical College of Fujian Medical University; Department of Emergency, Fujian Provincial Hospital, Fujian Provincial Emergency Center, Fuzhou, Fujian Province, China.
Neural Regen Res. 2020 Feb;15(2):324-331. doi: 10.4103/1673-5374.265563.
Emerging evidence suggests that bone marrow-derived mesenchymal stem cell transplantation improves neurological function after cardiac arrest and cardiopulmonary resuscitation; however, the precise mechanisms remain unclear. This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cell treatment on expression profiles of multiple cytokines in the brain after cardiac arrest and cardiopulmonary resuscitation. Cardiac arrest was induced in rats by asphyxia and cardiopulmonary resuscitation was initiated 6 minutes after cardiac arrest. One hour after successful cardiopulmonary resuscitation, rats were injected with either phosphate-buffered saline (control) or 1 × 10 bone marrow-derived mesenchymal stem cells via the tail vein. Serum S100B levels were measured by enzyme-linked immunosorbent assay and neurological deficit scores were evaluated to assess brain damage at 3 days after cardiopulmonary resuscitation. Serum S100B levels were remarkably decreased and neurological deficit scores were obviously improved in the mesenchymal stem cell group compared with the phosphate-buffered saline group. Brains were isolated from the rats and expression levels of 90 proteins were determined using a RayBio Rat Antibody Array, to investigate the cytokine profiles. Brain levels of the inflammatory mediators tumor necrosis factor-α, interferon-γ, macrophage inflammatory protein-1α, macrophage inflammatory protein-2, macrophage inflammatory protein-3α, macrophage-derived chemokine, and matrix metalloproteinase-2 were decreased ≥ 1.5-fold, while levels of the anti-inflammatory factor interleukin-10 were increased ≥ 1.5-fold in the mesenchymal stem cell group compared with the control group. Donor mesenchymal stem cells were detected by immunofluorescence to determine their distribution in the damaged brain, and were primarily observed in the cerebral cortex. These results indicate that bone marrow-derived mesenchymal stem cell transplantation attenuates brain damage induced by cardiac arrest and cardiopulmonary resuscitation, possibly via regulation of inflammatory mediators. This experimental protocol was approved by the Institutional Animal Care and Use Committee of Fujian Medical University, China in January 2016 (approval No. 2016079).
新出现的证据表明，骨髓间充质干细胞移植可改善心脏骤停和心肺复苏后的神经功能；然而，确切机制仍不清楚。本研究旨在探讨骨髓间充质干细胞治疗对心脏骤停和心肺复苏后大脑中多种细胞因子表达谱的影响。通过窒息诱导大鼠心脏骤停，并在心脏骤停6分钟后开始心肺复苏。心肺复苏成功1小时后，通过尾静脉给大鼠注射磷酸盐缓冲盐水（对照组）或1×10个骨髓间充质干细胞。采用酶联免疫吸附测定法测量血清S100B水平，并在心肺复苏后3天评估神经功能缺损评分以评估脑损伤。与磷酸盐缓冲盐水组相比，间充质干细胞组的血清S100B水平显著降低，神经功能缺损评分明显改善。从大鼠中分离出大脑，使用RayBio大鼠抗体阵列测定90种蛋白质的表达水平，以研究细胞因子谱。与对照组相比，间充质干细胞组中炎症介质肿瘤坏死因子-α、干扰素-γ、巨噬细胞炎性蛋白-1α、巨噬细胞炎性蛋白-2、巨噬细胞炎性蛋白-3α、巨噬细胞衍生趋化因子和基质金属蛋白酶-2的脑水平降低≥1.5倍，而抗炎因子白细胞介素-10的水平升高≥1.5倍。通过免疫荧光检测供体间充质干细胞，以确定它们在受损大脑中的分布，主要在大脑皮层中观察到。这些结果表明，骨髓间充质干细胞移植减轻了心脏骤停和心肺复苏诱导的脑损伤，可能是通过调节炎症介质实现的。本实验方案于2016年1月获得中国福建医科大学实验动物管理与使用委员会的批准（批准号：2016079）。
