目的 探讨调节性T细胞(regulatory T cells,Tregs)对于缺血缺氧性脑损伤(hypoxic-ischemic encephalopathy,HIE)小鼠神经系统功能远期行为学即学习、记忆功能的影响。方法 从24只小鼠随机抽取6只作为假手术(SHAM)组。剩余18只均使用Rice-Vannucci方法进行造模HIBD模型。造模前将18只小鼠随机分为实验组(HIBD)组、治疗(Tregs)组,耗竭(CD25)组,每组各6只。实验组正常造模;治疗组于造模后72 h内通过脑室注射Tregs;耗竭组在造模前1 d腹腔注射anti-CD25抗体。于造模及干预后对小鼠行为学进行统计分析。结果 造模后,与假手术组对比,其他组造模侧脑血流明显减少;水迷宫实验(Morris Water Maze)中,SHAM组与HIBD组、CD25组之间,Tregs组与HIBD组、CD25组之间在目标象限所待时长对比明显有延长;新物体识别(Novel Object Recognition)实验:SHAM组和HIBD组、CD25组相比较,Tregs组与HIBD组、CD25组相比,认知指数(recognition index,RI)有明显升高。结论 Tregs细胞在缺血缺氧性脑损伤的治疗中可以发挥神经保护作用。
Abstract
Objective To investigate the effect of regulatory T cells (Tregs) on the long-term behavior of neurological function in mice with hypoxic-ischemic encephalopathy (HIE), i. e. , learning and memory functions. Methods Six were randomly selected from 24 mice as the sham group. The remaining 18 models were modeled using the Rice-Vannucci method. Before modeling, 18 mice were randomly divided into experimental group (HIBD) group, treatment (Tregs) group, and depletion (CD25) group, with 6 mice in each group. The experimental group made normal molds; The treatment group was injected with Tregs through the ventricle within 72 hours after modeling. The depletion group was intraperitoneally injected with anti-CD25 antibody 1 day before modeling. Statistical analysis of mouse behavior was performed after modeling and intervention. Results After modeling, compared with the sham operation group, the cerebral blood flow on the side of the model was significantly reduced. In the water maze experiment (Morris Water Maze), the comparison of the waiting time in the target quadrant was significantly prolonged between the SHAM group and the HIBD group and the CD25 group, and between the Tregs group and the HIBD group and the CD25 group. Novel Object Recognition: Compared with the SHAM group, HIBD group, and CD25 group, the Tregs group had a significantly higher recognition index (RI) compared with the HIBD group and the CD25 group. Conclusion Treg cells can exert a neuroprotective effect in the treatment of ischemic-hypoxic brain injury.
关键词
缺血缺氧性脑病 /
调节性T细胞 /
脑室注射 /
行为学检测 /
水迷宫 /
新物体识别
Key words
ischemic-hypoxic encephalopathy /
regulatory T cells /
ventricular injection /
behavioral tests /
morris water maze /
novel object recognition
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基金
吴阶平基金“靶向抑制cGAS-STING-IRF3信号通路的新型纳米材料在新生儿缺血缺氧性脑病中的应用研究”(320.6750.2023-24-3)