人脐带来源间充质干细胞移植急性阿尔茨海默病模型小鼠引发的免疫应答反应

Immune response after transplantation of human umbilical cord-derived mesenchymal stem cells in a mouse model of acute Alzheimer's disease

背景：阿尔茨海默病患者的外周血和脑脊液中相应细胞因子浓度较正常人相比有明显的改变，加强了阿尔茨海默病伴随着免疫应答的结论，提示炎性应答可能参与了阿尔茨海默病神经改变的级联反应。目的：探讨人脐带间充质干细胞在急性阿尔茨海默病小鼠模型中引发的免疫应答反应与外周血中各细胞因子水平的关系。方法：取第5代人脐带间充质干细胞，调整细胞浓度为1×109 L-1待用。C57小鼠随机分为4组，间充质干细胞组侧脑室注射β-淀粉样蛋白1～42，尾静脉注射1 mL人脐带间充质干细胞；模型组侧脑室注射β-淀粉样蛋白1～42，尾静脉注射等体积生理盐水；生理盐水组不造模，尾静脉给予等体积的生理盐水；正常组不造模，不给予任何干预措施。结果与结论：与正常组相比，模型组小鼠在Morris水迷宫实验中逃避潜伏期延长、第一次穿环时间增加而穿环次数减少，间充质干细胞组小鼠逃避潜伏期有所减少，第一次穿环时间减少，穿环次数有所提高，但改善情况较模型组比较不明显。与正常组小鼠相比，模型组在造模后4 d出现N-乙酰天冬氨酸降低，肌醇升高，造模后7 d外周血炎性因子白细胞介素1β、肿瘤坏死因子α水平升高，白细胞介素10水平升高不明显；与模型组相比，注射脐带间充质干细胞7 d后外周血各炎性因子水平有所降低。结果表明人脐带间充质干细胞治疗阿尔茨海默病可能是通过调节免疫应答的途径来实现的。

BACKGROUND： Studies have demonstrated that concentration of cytokines in the peripheral blood and cerebrospinal fluid of Alzheimer＇s disease patients changes greatly compared with that in the healthy persons, which adds evidence to the conclusion that Alzheimer＇s disease is followed by immune response. This suggests that inflammatory response possibly participates in the cascade reaction of neuropathy in Alzheimer＇s disease. OBJECTIVE： To investigate the relationship between immune response and the level of each cytokine in the peripheral blood in a mouse model of Alzheimer＇s disease after transplantation of human umbilical cord mesenchymal stem cells （hUCMSCs）. METHODS： Passage 5 hUCMSCs at a density of 1×109/L were prepared for use. C57 mice were randomly divided into four groups. In the hUCMSCs group, lateral ventricle injection of β-amyloid 1-42 and caudal vein injection of 1 mL hUCMSCs were performed. In the model group, lateral ventricle injection of β-amyloid 1-42 and caudal vein injection of 1 mL physiological saline were performed. In the physiological saline group, Alzheimer＇s disease was not induced, but equal amounts of physiological saline were administered via the caudal vein. In the normal group, Alzheimer＇s disease was not induced, and no treatment was given. RESULTS AND CONCLUSION： Morris water maze test results showed that compared with normal group, escape latency was prolonged, and the time spent in passing through the platform for the first time was increased, while the number that mice crossed through the platform was decreased in the model group. Compared with the model group, the escape latency was slightly shortened, the time spent in passing through the platform for the first time was decreased, and the number that mice crossed through the platform was slightly, but not significantly, increased in the hUCMSCs group. Compared with the normal group, N-acetylaspartic acid was decreased and myo-inositol was increased at 4 days after Alzheimer＇s disease induction, and interleukin 1β, tumor necrosis factor-α in the peripheral blood were increased, but the increase in interleukin 10 was not obvious at 7 days after Alzheimer＇s disease induction in the model group. Compared with the model group, level of each cytokine was decreased at 7 days after hUCMSCs injection. These results suggest that hUCMSCs for treatment of Alzheimer＇s disease is implemented by regulation of immune response.