摘要
肥胖与糖尿病、高血压、心绞痛和关节炎等多种疾病有关,已成为日益严重的全球性公共健康问题。慢性低度炎症和免疫系统激活参与肥胖相关胰岛素抵抗发病机制。胰岛素是唯一可降低血糖的激素,通过胰岛素信号通路发挥作用。正常情况下,机体促炎系统和抗炎系统通过相互作用维持机体免疫平衡。促炎和抗炎反应动态平衡决定了炎症发生、发展与结局。炎症信号通路激活可诱导中枢和外周组织胰岛素抵抗,Toll样受体4(TLR4)介导的信号通路是产生促炎反应的重要通路之一。已知高脂饮食与慢性低度炎症过程有关,饱和脂肪酸可激活TLR4受体,刺激炎症细胞因子表达,抑制胰岛素信号传导。抗炎系统中,胆碱能抗炎途径(CAP)是一条神经免疫调节途径,具有快速、可逆、准确且能适应炎症输入信号变化等特点,主要由迷走神经、脾脏与脾交感神经、乙酰胆碱和α7烟碱型乙酰胆碱受体(α7nAChR)组成,CAP激活可改善肥胖诱导的炎症和胰岛素抵抗。本文围绕肥胖介导的炎症、CAP抗炎途径及其与胰岛素抵抗的关系进行综述,丰富胰岛素抵抗的分子免疫机制,为胰岛素抵抗相关疾病抗炎诊疗研究提供基础。
Obesity is related to many diseases,such as diabetes,hypertension,angina pectoris and arthritis,and has become an increasingly serious global public health problem.Chronic low-grade inflammation and activation of immune system are involved in pathogenesis of obesity-related insulin resistance.Insulin is only hormone that can lower blood sugar,and works through insulin signaling pathway.Under normal circumstances,interaction of pro-inflammatory and anti-inflammatory system maintains immune homeostasis.Dynamic balance of pro-inflammatory and anti-inflammatory reactions determines occurrence,development and outcome of inflammation.Activation of inflammatory signaling pathways can induce insulin resistance in central and peripheral tissues,and Toll-like receptor 4(TLR4)signaling pathway is one of important pathways that produce pro-inflammatory responses.It has known high-fat diet is associated with chronic low-grade inflammation,which may due to saturated fatty acids activate TLR4 receptors,stimulate expression of inflammatory cytokines,and inhibit insulin signal transduction.In anti-inflammatory system,cholinergic anti-inflammatory pathway(CAP)is a neuroimmunological regulation pathway,which is fast,reversible,accurate and can adapt to changes in inflammatory input signals,which is mainly composed of vagus nerve,spleen and splenic sympathetic nerve,acetylcholine andα7 nicotinic acetylcholine receptor(α7nAChR).Activation of CAP can improve obesity-induced inflammation and insulin resistance.This review focus on obesity-mediated inflammation,CAP anti-inflammatory pathways,and their relationship with insulin resistance,in order to enrich molecular immune mechanism of insulin resistance,and provide a basis for research of anti-inflammatory diagnosis and treatment of insulin resistance-related diseases.
作者
周璐瑾
刘新月
常晓彤
ZHOU Lujin;LIU Xinyue;CHANG Xiaotong(Department of Key Laboratory of Clinical Laboratory,Hebei North University,Zhangjiakou 075000,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2024年第4期888-893,共6页
Chinese Journal of Immunology
基金
河北省高等学校科学技术研究重点项目(ZD2018076)
河北北方学院自然科学项目(YB2020012)。
关键词
胰岛素抵抗
炎症信号通路
胆碱能抗炎途径
Insulin resistance
Inflammation signaling pathway
Cholinergic anti-inflammatory pathway
