精神心理应激可导致肠易激综合征（IBS）症状发生或复发。应激如何诱发IBS内脏高敏感（VH）的详尽机制不明。我们通过急性避水应激大鼠结肠VH的预实验发现，阻断糖皮质激素膜受体（mGR）相关联的瞬时受体电位离子通道M8（TRPM8）可抑制VH形成；文献报道，富含脯氨酸的非受体酪氨酸激酶2（Pyk2）在皮质酮快速作用中发挥核心作用。我们推测mGR/Pyk2/TRPM8通路参与介导了急性应激引发的结肠VH。本项目的内容和目标是：①证实急性应激致结肠VH的机制中有mGR/Pyk2/TRPM8信号通路的参与；②证实Pyk2被PKA、PI3K/Akt和PKC共同激活是皮质酮通过TRPM8快速作用的必要条件；③证实TRPM8细胞膜嵌入是上述机制的关键环节。本研究对探明精神因素导致或加重IBS发病机制有理论和实践意义。

Mental stress could play an important role in the development and recurrence of irritable bowel syndrome (IBS). However, the mechanisms underlying stress-induced visceral hypersensitivity (VH), the key pathophysiological factor of IBS, are still not completely understood. Our experiments showed that blocking the membrane-bound glucocorticoid receptors (mGR) related transient receptor potential melastatin 8 (TRPM8) could inhibit the acute water avoidance stress (WAS)-induced VH. It has been proved that non-receptor proline-rich tyrosine kinase 2 (Pyk2) plays a key role in modulating the rapid action of corticosterone. Thus it is estimated that mGR/Pyk2/TRPM8 might take part in the acute stress-induced VH. The aims of this project are to prove: 1) mGR/Pyk2/TRPM8 take part in the acute stress induced VH; 2) Pyk2 triggered by simultaneous activation of PKA, PI3K/Akt and PKC pathways lead to the rapid action of corticosterone. 3)TRPM8 insertion is the key part of the above mechanism. This study will provide new clues about the mechanisms underlying the mental stress-induced VH in IBS.