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.
Abstract
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 inflamma-tion.Activation of inflammatory signaling pathways can induce insulin resistance in central and peripheral tissues,and Toll-like recep-tor 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 and α7 nicotinic acetyl-choline 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.
基金项目
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)
国家科技期刊平台
NSTL
万方数据