TGF-β与Notch信号cross-talk调控气道高反应Treg/Th17平衡机制及针刺的作用

气道高反应患者易在麻醉期间发生呼吸道痉挛和气道水肿，严重影响临床麻醉安全。既往研究证实T淋巴细胞在气道高反应进程中起着重要作用，但具体机制不明。本课题组前期研究证实针刺可明显改善气道高反应性，机制与调控Notch信号介导CD4+T淋巴细胞Th17/Treg表达平衡有关；同时，TG-β也在调控Treg/Th17平衡中发挥了关键作用，可能与Notch信号协同调控Th17/Treg平衡有关。据此推测针刺改善气道高反应性与TGF-β与Notch信号的cross-talk机制维持Treg/Th17平衡有重要因果关系。为了验证上述假设，本课题拟通过动物及体外实验，正向分析和反向验证相结合证实TGF-β与Notch信号交联调控Treg/Th17平衡在气道高反应中的机制；并进一步通过基因敲除等技术探讨针刺在TGF-β与Notch交联中的作用，以期为针刺改善围术期气道高反应提供新的机制及实验依据。

Airway hyperreaction intends to lead bronchospasm and airway obstruction during the perioperative anesthesia, which even impact on clinical anesthesia safely. Studies have shown that T lymphocytes plays an important role in pathogenesis of airway hyperresponsiveness, but the concrete mechanism is unknown. Our previous studies demonstrated that acupuncture can imbalance Thl7/Treg during hyperreaction, mediated by expression of Notch signaling; TGF-β is the foothold of regulation of Treg/Th17, which may cooperate with Notch signal in regulating Thl7/Treg. So we hypothesized that Acupuncture can balance Treg/Th17 by regulating TGF-β and Notch signaling. To verify the above hypothesis, study on the forward analysis and backward verification combination, to confirm that TGF-β crosstalk with Notch signaling regulate Treg/Th17 balance mechanism in vitro. And on this basis, through the gene knockout technology, further analyze the mechanism of mediate the balance of Treg/Th17 by TGF-β and Notch cross-talk with airway hyperresponsiveness and the intervention of acupuncture. This task try to provide new mechanisms and experimental evidence for acupuncture to improve airway hyperresponsiveness during perioperative.