探讨IL-17中和在自发性脑出血患者神经功能和神经干细胞定向分化的作用

探讨IL-17中和在自发性脑出血患者神经功能和神经干

细胞定向分化的作用

目的

自发性脑出血(sICH)是一系列严重的高起病率、高致死、致残率的脑血管事件。在实验动物模型和细胞水平上，最新研究发现IL-17细胞因子与sICH的发病机制关系密切。此次研究的目的主要是阐明IL-17对sICH患者的在神经功能的临床价值和作用机制。

方法

我们对45例重度脑出血患者以及45例正常健康人的血清IL-17水平进行动态的检测，我们采用建立完善的临床量表对自发性脑出血病人的神经功能损伤程度和神经功能恢复的状况进行详细评估并打分。分别对不同分组的实验小鼠的神经功能损伤进行详细的分析和评价。在此同时，建立细胞再生体系/共培养体系，根据组成成分不同将其分成三组，第一组是NSC培养体系,第二组是NSC+ TCRγδ细胞组，第三组是NSC + TCRγδ细胞+ IL-17中和组。最后我们通过相关实验仪器测试了NSCs（神经干细胞）分化、nestin(巢蛋白)、GFAP（胶质纤维酸性蛋白）和MAP2（成熟神经元特异性标志物）的细胞存活率和不同的生物标志物。

结果

sICH患者血清中的IL-17水平含量与自发性脑出血病人神经功能恢复相互之间呈显著负相关，(p<0.001)。在细胞水平研究中，结果表明在细胞培养/共同培养体系中，IL-17中和可能会促进NSC的生存能力，这种NSC的生存能力将受到TCR γδ+共培养体系的影响(p = 0.031) ，TCRγδ细胞共培养的条件下NSCs存活率明显降低(p = 0.023)，差异有统计学意义，研究结果认为IL-17中和提高NSC定向分化为星形胶质细胞，而不是定向分化神经元细胞。

结论

IL-17作为一种促进炎症反应的细胞因子，这种细胞因子具有非常强烈的神经细胞毒性作用，这种神经细胞毒性作用显著影响着sICH患者的神经功能恢复状况。可能是由于IL-17促炎因子抑制了NSC向功能神经细胞的分化从而影响病人预后的

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功能恢复。实验研究得出IL-17中和的功能会削弱IL-17促炎因子抑制作用，IL-17中和不仅可以加强NSCs的定向分化水平，并且可以显著的促进神经功能的恢复。

关键词脑内出血；神经干细胞；白介素17；中和；定向分化

AbstractObjective To investigate the effect of IL-17 on neural

function and neural stem cell differentiation in patients with

spontaneous intracerebral hemorrhage

Objective spontaneous intracerebral hemorrhage (sich) is a series of severe cerebrovascular events with high morbidity, mortality and disability. at the experimental animal model and cell level, recent studies have found that il-17 cytokines are closely related to the pathogenesis of sich. the aim of this study was mainly to elucidate the clinical value and mechanism of il-17 in neurofunction in patients with sich.

Methods we performed a dynamic test of serum il-17 levels in 45 patients with severe intracerebral hemorrhage and in 45 normal and healthy patients. we used a well-established clinical scale to evaluate the degree of neurological impairment and neurological recovery in patients with spontaneous intracerebral hemorrhage in detail and rated. The neurological damage of different groups of experimental mice was analyzed and evaluated in detail. At the same time, the cell regeneration system / co-culture system was established, which was divided into three groups according to the composition, the first group was NSC culture system, the second group was NSCTCR \947;δcell group, the third group was NSCTC il-17 neutralization group in r\947;δcells. finally, we tested the cell viability and different biomarkers of nscs (neural stem cells) differentiation, nestin (nestin), gfap (glial fibroacid protein), and map2(mature

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neuron-specific marker) through relevant experimental instruments.

Result There was a significant negative correlation between serum IL-17 levels in sICH patients and neurological recovery in patients with spontaneous intracerebral hemorrhage (p<0.001). the results suggest that IL-17 neutralization may promote NSC viability in cell culture/co-culture systems, which will be affected by TCRγδco-culture systems (p =0.031). The survival rate of NSCs was significantly decreased (p =0.023) under co-culture of TCR \947;δcells.the results suggest that IL-17 neutralization enhances directional differentiation into astrocytes rather than directed differentiation of neurons.

Conclusions IL-17 as a cytokine promoting inflammatory response, this cytokine has a very strong neurocytotoxic effect, which significantly affects the neurological recovery status of sICH patients. probably because IL-17 proinflammatory factors inhibit the differentiation of NSC to functional nerve cells and thus affect the functional recovery of patient prognosis. The IL-17 neutralizing function can weaken IL-17 pro-inflammatory factor inhibition, IL-17 neutralizing can not only strengthen the NSCs differentiation level, but also promote the recovery of nerve function.

[Key words] Intracerebral hemorrhage; neural stem cells; interleukin 17; neutralization; directional differentiation

探讨IL-17中和在自发性脑出血患者神经功能和神经干

细胞定向分化的作用

1 前言

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