基于肠道菌群- Treg/γδT细胞-IL-17免疫炎症信号通路的电针抗缺血性脑损伤机制研究

T cell-mediated inflammatory signaling is involved in all stages of the ischemic cascade, from the early damaging events triggered by arterial occlusion to the late regenerative processes underlying post-ischemic tissue repair. Acupuncture is regarded as a potent method to reduce inflammatory response after stroke, but how it exerts this effect is kept unknown. The latest research showed that commensal microbiota reduced ischemic brain injury by regulating intestinal Treg/γδTcell-IL-17 signaling. This is similar with the traditional Chinese medicine theory “Fudichouxing” which means benefiting brain injury by improving intestinal dysfunction. Our previous study showed that the KEGG pathways of ischemic-induced upregulated and acupuncture down-regulated gene were mainly involved in immunoinflammatory response; Gene differential expression analysis showed that a lot of IL-17-related pro-inflammatory factors, inflammatory factors and their receptors were significantly up-regulated by ischemia, however, acupuncture treatment can reverse it. In addition, we also found that acupuncture can significantly improve MCAO rat intestinal propulsion. Based on the above evidence, we will apply neurobiological, flow cytometry, second-generation sequencing, fluorescent tracer, fecal transplantation and common molecular biology techniques to reveal the role of intestinal flora-Treg/γδTcell-IL-17 signaling pathway in the anti- inflammatory effect of acupuncture on stroke. This study will provide scientific evidences for acupuncture treatment as an effective therapeutic approach for brain injury by the perspective of gut-brain axis regulation.

T细胞介导的炎症反应贯穿于缺血性中风的各个阶段；针刺治疗可有效减轻中风后炎性反应，但针刺治疗如何干预脑内炎性因子的表达却仍不明确。最新研究显示肠道菌群可通过Treg/γδT细胞-IL-17信号通路减轻中风后免疫炎性反应及病理损害。这与中医“釜底抽薪”治疗极其相似。本课题组前期研究发现中风后缺血侧脑组织内上调而电针治疗后下调的基因主要集中在与免疫炎症反应相关的信号通路上；差异基因分析也发现缺血脑组织内多种IL-17相关的炎性因子及其受体表达明显上调，电针治疗可逆向调节其表达。此外，针刺还可显著提高MCAO大鼠肠道推进力。基于以上证据，本课题拟以缺血性脑中风模型为载体，运用神经生物学、二代测序及粪便移植术等实验技术，从肠道菌群- Treg/γδT细胞-IL-17免疫炎症信号通路入手揭示针刺抗中风后脑内炎性反应机制；将脑-肠轴调控机制引入到针刺抗脑损伤研究，为针刺抗脑损伤的临床运用提供实验依据。

T细胞介导的炎症反应贯穿于缺血性中风的各个阶段；针刺治疗亦被证实可有效减轻中风后炎性反应。但针刺治疗如何干预脑内炎性因子的表达却仍不明确。最新研究显示肠道菌群可通过Treg/γδT细胞-IL-17信号通路减轻中风后免疫炎性反应及病理损害。这与中医“釜底抽薪”治疗极其相似。本课题组以缺血性脑中风模型为载体，运用神经生物学、二代测序及粪便移植术等实验技术，从肠道菌群- Treg/γδT细胞-IL-17免疫炎症信号通路入手揭示针刺抗中风后脑内炎性反应机制；结果显示，针刺治疗可改善中风后肠道菌群紊乱及肠道内短链脂肪酸的生成，提高中风大鼠小肠推进力增加肠道屏障致密性，减少小肠内炎性因子的表达，改善中风大鼠肠道及脑组织病理损伤，这一过程可能与针刺调节肠道及脑内Treg/γδT细胞平衡，减少肠源性促炎细胞向脑迁移，从而下调IL-17炎性信号通路相关。本研究将脑-肠轴调控机制引入到针刺抗脑损伤研究，为针刺在中风早期的临床应用提供实验依据。