下丘脑-垂体-肾上腺皮质（HPA）轴对维持体内正常能量代谢至关重要，其功能异常与2型糖尿病（T2DM）发病及进展相关。此外，下丘脑配体门控离子通道参与调控HPA轴功能。然而，糖尿病状态下HPA轴功能异常的机制尚不清楚。我们前期研究表明：大鼠下丘脑室旁核（PVN）中促肾上腺皮质激素释放激素（CRH）细胞表达酸敏感离子通道1a亚型（ASIC1a）；阻断ASIC通道下调糖尿病大鼠HPA轴活性、降低血糖。据此，我们提出如下假说：下丘脑ASIC1a通过削弱糖皮质激素（GC）对PVN中CRH负反馈调节，参与调控T2DM状态下HPA轴功能异常。为验证这一假说，我们将研究糖尿病状态下PVN中ASIC1a在HPA轴功能异常中的作用及对血糖的影响，在GC负反馈调节HPA轴中的作用，以及对PVN中CRH神经元的调控。本研究将有助于更进一步理解糖尿病状态下HPA轴功能异常的机制，为干预T2DM提供新的理论依据。

The hypothalamus-pituitary-adrenocortical (HPA) axis serves an important role in maintaining energy homeostasis. Dysfunction of HPA axis is relevant to the onset and development of type 2 diabetes mellitus (T2DM). Ligand-gated ion channels in the hypothalamus regulate the activity of HPA axis. However, the detailed mechanism of the dysfunction of HPA axis in diabetes remains unclear.Our preliminary studies showed that the corticotropin-releasing hormone (CRH) neuron in the paraventricular nucleus (PVN) of the hypothalamus expressed acid-sensing ion channel (ASIC) 1a subtype in the rat. Moreover, inhibiting ASIC channel reduced the activity of HPA axis and lowered blood glucose. Therefore, we hypothesize that the involvement of ASIC1a in the diminished glucocorticoid（GC）negative feedback inhibition on CRH in the PVN contributes to the dysfunction of HPA axis in T2DM. To explore this hypothesis, we plan to study the influence of ASIC1a in the PVN on the activity of HPA axis and blood glucose in T2DM, the role of ASIC1a in the negative feedback inhibition on HPA axis by GC, and the modulation of ASIC1a on the CRH neuron. The findings from this study will contribute to elucidating the molecular and cellular mechanisms of dysfunction of HPA axis in diabetes, providing a new strategy for the intervention of T2DM.