脊髓小胶质细胞GLP-1受体/IL-10/β-内啡肽通路及其与独一味镇痛作用的关系

Spinal GLP-1 Receptor/IL-10/β-endorphin Pathway and It′s Relation with Lamiophlomis rotate Analgesia

GLP-1受体是B族G-蛋白偶联受体,主要分布于胰岛、肺、胃、小肠、肾脏、心脏和中枢神经系统。GLP-1受体在外周通过促进血糖依赖式的胰岛素分泌和增加胰岛素敏感性参与血糖调节,在中枢神经系统参与神经保护和镇痛。本文简述我们实验室最近发现的脊髓小胶质细胞GLP-1受体/IL-10/β-内啡肽通路及其与一些中草药镇痛作用之间的关系。GLP-1,艾塞那肽和WB4-24激动脊髓GLP-1受体,通过c AMP/PKA/p38β/CREB信号转导通路合成/表达IL-10,后者通过自分泌方式活化IL-10受体/STAT3通路合成/表达β-内啡肽,从而在多种慢性疼痛模型产生显著镇痛作用。止痛中草药独一味通过激动脊髓背角小胶质细胞GLP-1受体/β-内啡肽通路产生镇痛作用。以山栀子苷为代表的环烯醚萜苷包括京尼平苷、马钱子苷、梓醇和莫诺苷,是人和大鼠GLP-1受体正构性激动剂。这些研究结果提示,脊髓GLP-1受体/IL-10/β-内啡肽通路可能是已被人体证明有效的治疗慢性疼痛新靶点。

Glucagon-like peptide-1（GLP-1）receptors belong to the class B of G protein coupled-receptors and are expressed in pancreas,lungs,GI tract,kidneys,heart and the central nervous system. During episodes of hyperglycemia activation of GLP-1 receptors located on pancreas islet β-cells facilitates insulin release and increases insulin sensitivity to regulate blood sugar. In the central nervous system,activation of GLP-1 receptors produces neuroprotection and analge-sia. In this mini-review,we have summarized our recent work：1）identification of microglial GLP-1 receptor/IL-10/β-endorphin pathway in the spinal cord;2）discovery of the mechanisms of activation of GLP-1 receptors by which analgesic Lamiophlomis rotata and its effective ingredients iridoid glycosides produce antinociception. Our work highlight that spinal microglial GLP-1 receptor might be a human-demonstrated target for the treatment of chronic pain.