棕榈酸诱导胰岛β细胞氧化应激和内质网应激的研究进展  

Research Progress of Palmitic Acid Induced Oxidative Stress and Endoplasmic Reticulum Stress on Islet β Cell

作　　者：张茜 王瑞 于智超 张硕 黄延芹[3] ZHANG Xi;WANG Rui;YU Zhichao;ZHANG Shuo;HUANG Yanqin(College of Traditional Chinese Medicine,Shandong University of Traditional Chinese Medicine,Jinan 250014,China;Shandong Collaborative Innovation Center for Classic and Famous Prescriptions of Traditional Chinese Medicine,Jinan 250355,China;The Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250011,China)

机构地区：[1]山东中医药大学中医学院,济南250014 [2]山东省中医经典名方协同创新中心,济南250355 [3]山东中医药大学附属医院,济南250014

出　　处：《激光生物学报》2023年第2期118-125,共8页Acta Laser Biology Sinica

基　　金：国家自然科学基金面上项目(81974562,81603613);济南市科技创新发展计划项目(202019029);钱秋海全国名老中医药专家传承工作室建设项目(国中医药人教函[2022]75号);山东省泰山学者工程专项项目(tsqn202211354)。

摘　　要：2型糖尿病(T2DM)主要由胰岛β细胞的胰岛素分泌缺陷和胰岛素抵抗引起。棕榈酸作为人体内最丰富的游离脂肪酸之一,其体内含量过高易造成脂代谢紊乱,诱导胰岛β细胞功能障碍及胰岛素抵抗。这与T2DM的发生发展密切相关,但具体机制尚未完全明确。棕榈酸诱导胰岛β细胞发生的氧化应激和内质网应激(ERS)是影响胰岛β细胞功能以及破坏胰岛素信号传导的关键应激途径。棕榈酸通过增加线粒体氧化、二酰基甘油-蛋白质激酶C-还原型辅酶Ⅱ途径、改变线粒体呼吸链正常功能和炎症刺激加重氧化应激,通过影响内质网折叠能力、破坏胞内蛋白运输途径、上调未折叠蛋白反应相关转录因子、棕榈酰化、降解羧肽酶E和减少内质网中Ca^(2+)促进ERS,加剧胰岛β细胞功能障碍和凋亡,最终导致T2DM的发生与发展。本文综述了棕榈酸与胰岛β细胞内氧化应激和ERS的关联性,介绍了蛋白激酶R抑制剂、人参皂苷Rg1和三黄汤等具有潜力的中、西医靶向干预药物,为T2DM的临床治疗提供新思路。Type 2 diabetes mellitus(T2DM) is mainly caused by defective insulin secretion and insulin resistance of islet βcells. Palmitic acid is one of the most abundant free fatty acids in the human body. When its content in the body is too high, it is easy to cause lipid metabolism disorder and induce islet β cells dysfunction and insulin resistance, which are closely related to the occurrence and development of T2DM. However, the specific mechanism is not precise. The function of islet β cells could be affected by oxidative stress and endoplasmic reticulum stress(ERS) induced by palmitic acid. It is also the critical pathway for destroying insulin signaling. Palmitic acid aggravates oxidative stress by increasing mitochondrial oxidation, diacyl glycerol-protein kinase C-nicotinamide adenine dinucleotide phosphate pathway, changing the normal function of the mitochondrial respiratory chain and inflammatory stimulation. It also affects the folding ability of the endoplasmic reticulum, destroys the intracellular protein transport pathway, upregulates unfolded protein response-related transcription factors, makes palmitoylation,degrades carboxypeptidase E, and reduces Ca^(2+) in the endoplasmic reticulum to promote ERS. Both promote islet β cells dysfunction and apoptosis, ultimately leading to the occurrence and development of T2DM. This paper reviewed the relationship between palmitic acid and islet β cells, the correlation between intracellular oxidative stress and ERS and the potential Chinese and Western medicine-targeted intervention drugs such as protein kinases R inhibitor, Ginsenoside Rg1 and Sanhuang Decoction. It would provide a novel idea for the clinical treatment of T2DM.

关 键 词：胰岛Β细胞 2型糖尿病 棕榈酸 氧化应激 内质网应激 

分 类 号：R587.1[医药卫生—内分泌]