Immunomodulatory effects of T helper 17 cells and regulatory T cells on cerebral ischemia.
Immunomodulatory effects of T helper 17 cells and regulatory T cells on cerebral ischemia.
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发表时间：
2018
影响因子：
3.2
通讯作者：
Y. Zheng;T. Song;Ll Zhang;N. Wei
中科院分区：
文献类型：
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作者：
Y. Zheng;T. Song;Ll Zhang;N. Wei
本研究旨在分析脑缺血与免疫效应的关系。将70只昆明种小鼠随机分为模型组（60只）和假手术组（10只）。模型组按给药时间分为6 h、12 h、24 h、48 h、72 h和5 d 6个亚组，每组10只。采用线栓法建立小鼠暂时性大脑中动脉闭塞（tMCAO）模型。采用神经功能缺损评分（NDS）评价脑损伤程度。脑缺血再灌注后，脑组织水肿加重，梗死面积增大。48h脑梗死体积达高峰（44.4 ± 3.2%），随后逐渐减少。NDS评分逐渐降低，神经功能逐渐恢复。在6 h时，NDS评分为4.6 ± 0.55，而在5 d时间点，其显著降低（P <0.05）至2.2 ± 0.45。流式细胞仪分析显示，缺血后Th17细胞百分比逐渐升高。24 h时，Th17细胞百分率达到最大值（0.70 ± 0.10%），与假手术组和5 d组比较差异有统计学意义（P <0.05）。24 h时Th17细胞百分率最低（0.9 ± 0.29%），5 d时Th17细胞百分率较正常水平显著升高（3.2 ± 0.49%）（P <0.05）。Th17和Treg相关细胞因子的分泌与缺血后Th17和Treg细胞的数量一致。然而，脑组织和血清中IL-17A的水平表明随着缺血时间的延长而增加的趋势。该标志物在第5天达到最高水平。脑IL-17含量为77.9 ± 5.11pg/ml，血清IL-17含量为29.44 ± 3.06pg/ml。Th17和Treg相关炎性细胞因子分泌的变化与Th17和Treg细胞比例的变化一致。两组之间的显著相关性和缺血性脑损伤的程度。提示脑缺血后Th17/Treg细胞功能失衡。
The aim of the present study was to analyze the relationship between cerebral ischemia and immune effects. A total of 70 Kunming mice were randomly divided into two groups: a model group (60 mice) and a sham group (10 mice). The model group was divided into six subgroups (10 mice per group) which were categorized according to the following time periods of treatment: 6 h, 12 h, 24 h, 48 h, 72 h and 5 days. The temporary middle cerebral artery occlusion (tMCAO) mouse model was established using intracavitary suture. The degree of brain injury was evaluated by detecting the neurological deficit score (NDS). Following cerebral ischemia reperfusion, the edema of the brain tissue was aggravated, and the infarction area was increased. At 48 h, the volume of the cerebral infarction reached a peak (44.4±3.2%) and then it decreased. The NDS score gradually decreased, and the nerve function was gradually restored. At 6 h, the NDS score was 4.6±0.55, whereas at the 5 d time point, it was significantly decreased (P less than 0.05) to 2.2±0.45. Flow cytometry analysis indicated that the percentage of Th17 cells increased gradually following ischemia. At 24 h, the percentage of Th17 cells reached its maximum value (0.70±0.10%) compared with the sham and the 5 d groups (P less than 0.05). At 24 h, the percentage of Th17 cells reached the lowest value (0.9±0.29%), whereas at the 5 d time point it increased significantly (3.2±0.49%) compared with the normal level (P less than 0.05). The secretion of Th17 and Treg-associated cytokines was consistent with the number of Th17 and Treg cells following ischemia. However, the levels of IL-17A in the brain tissues and the serum indicated a tendency to increase following the prolongation of ischemia. This marker reached the maximum levels on day 5. The IL-17 brain level was 77.9±5.11pg/ml, whereas the serum level was 29.44±3.06pg/ml. The changes in the secretion of the Th17 and Treg-related inflammatory cytokines were consistent with the changes in the cell ratio of Th17 and Treg cells. A significant correlation was noted between the two groups and the degree of ischemic brain injury. The results suggested that the functional status of Th17/Treg cells was imbalanced following cerebral ischemia.