理学院“科学沙龙”系列学术报告会（刘庆平 教授）
广东省海洋生物技术重点实验室-系列学术讲座
省市共建海洋灾害预警与防护广东省重点实验室—系列讲座
报告题目：靶向病理性血管疾病药物研究及其在临床诊断与治疗中的应用
报 告 人：刘庆平 教授
报告时间：2024年5月25日（星期六）上午10:30
报告地点：教学楼D座409
报告人简介：汕头大学香港中文大学联合汕头国际眼科中心教授、汕头大学医学院眼科研究所副所长；辽宁省糖脂代谢研究重点实验室主任；2013-2017年教育部教学指导委员会委员；国家自然科学基金委员会评审专家及第十三、四届专家评审组会评专家；教育部学位与研究生教育中心第三轮、第四轮学科评估专家；国际科技合作计划同行专家；有40余年医学生物学相关研发经验，曾主持国家自然科学基金5项，辽宁省广东省自然科学基金和重点专项基金7项，参与日本文部省与厚生省多项研究项目；期刊发表论文230余篇，授权5项发明专利。
主要研究方向：
1、 动脉粥样硬化及血栓形成细胞信号传导机理研究
2、 脂毒性代谢紊乱跨器官导致眼科疾病发生的机理研究
3、 基因工程重组蛋白靶向脂毒性配体药物研究。
4、 脂类活性衍生物降血脂研究与新化合物开发。
5、 心脑血管疾病标志性病原危险因子发现与检测研究与开发
6、 眼科疾病脂质代谢标志物发现与特异性诊断研究与开发
报告摘要：
脂质代谢平衡紊乱所波及的相关疾病已对人类健康造成巨大威胁。最典型的脂质代谢疾病-心血管疾病（cardiovascular disease；CVD）2020年《中国心血管健康与疾病报告》心脑血管患病率及死亡率再次成为城乡居民总死亡原因的首位。非酒精性脂肪性肝病（Non-alcoholic fatty liver disease ；NAFLD）是一种肝细胞脂肪变性和蓄积为特征的临床病理综合征，其临床进展与脂质代谢紊乱（Lipid metabolism disorder）等代谢性危险因素强烈并存，强烈相关于心血管事件。眼部小动脉血管由于处于相对循环末端因此也是最为脆弱的动脉血管，是临床上唯一可以通过肉眼进行判断动脉硬化的血管。来自于全身性脂质代谢紊乱同样波及到眼部。氧化低密度脂蛋白 （oxidized low density lipoprotein, oxLDL）在动脉粥样硬化AS中破坏血管内皮细胞导致单核巨噬细胞侵润，炎性极化是脂毒性炎症的关键环节。最近我们继NAFLD之后，在开角型青光眼（POAG）和年龄相关性黄斑变性（AMD）中再次发现高浓度oxLDL和CD36受体基因高表达共存，提示脂毒性oxLDL以血液循环为致病媒介致全身多器官脂质异位沉积代谢平衡紊乱。oxLDL-巨噬细胞-CD36轴引发的脂质代谢紊乱从AS扩展到NAFLD再到眼部炎症，可能是众多跨器官炎症疾病交叉的独立危险因素。oxLDL跨器官时空调控可能引发了同一类群单核细胞趋向性募集，形成多器官巨噬细胞脂毒性炎症分子表观调控轴，引发病理性血管性疾病。为此本项目拟以oxLDL的ω-COOH结构为特征的诱导下，分析探讨动脉粥样硬化（AS）、非酒精性脂肪肝（NAFLD）以及眼部巨噬细胞分子表观的同质性特征群；以重组蛋白短肽特异性靶向oxLDL蛋白ω-COOH，探讨同质巨噬细胞分子表观重编程保护机制，为全身脂毒性炎症“一因多果，多病同治”提供新的理论实验依据和治疗思路。
ABSTRACT
The related diseases caused by the disorder of lipid metabolism balance have caused great threat to human health. The most typical disease of lipid metabolism - cardiovascular disease; In the 2020 China Cardiovascular Health and Disease Report, cardiovascular and cerebrovascular morbidity and mortality once again ranked first among the total causes of death for urban and rural residents. Non-alcoholic fatty liver disease (non-alcoholic fatty liver disease; NAFLD is a clinicopathological syndrome characterized by fatty degeneration and accumulation of hepatocytes. Its clinical progression is strongly correlated with metabolic risk factors such as Lipid metabolism disorder, and is strongly associated with cardiovascular events. Ocular arteriole vessels are the most fragile arteries because they are at the end of relative circulation, and are the only vessels that can be used to judge atherosclerosis clinically by the naked eye. Systemic lipid metabolism disorders also affect the eyes. oxidized low density lipoprotein (oxLDL) destroys vascular endothelial cells in atherosclerotic AS resulting in mononuclear macrophage invasion, and inflammatory polarization is a key link in lipotoxic inflammation. Recently, following NAFLD, we once again found the coexistence of high concentration of oxLDL and high expression of CD36 receptor gene in open Angle glaucoma (POAG) and age-related macular degeneration (AMD), suggesting that lipotoxic oxLDL may cause the imbalance of lipid ectopic deposition metabolism in multiple organs of the body through blood circulation as a pathogenic medium. The expansion of lipid metabolism disorder from AS to NAFLD to ocular inflammation induced by the OXLDL-macrophage-CD36 axis may be an independent risk factor for cross-organ inflammatory diseases. The temporal and spatial regulation of oxLDL across organs may trigger the selective recruitment of monocytes of the same group, forming an apparent regulatory axis of lipotoxic inflammatory molecules in multi-organ macrophages, leading to pathological vascular diseases. In this study, the ω-COOH structure of oxLDL was used to analyze and explore the molecular apparent homogeneity of atherosclerosis (AS), non-alcoholic fatty liver (NAFLD) and ocular macrophages. The recombinant protein short peptide specifically targeted oxLDL protein ω-COOH to explore the molecular apparent reprogramming protection mechanism of homogenous macrophages, providing a new theoretical experimental basis and treatment idea for systemic lipotoxic inflammation "one cause and multiple fruits, multiple diseases and the same treatment".
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汕头大学海洋与生命学科
广东省海洋生物技术重点实验室
省市共建海洋灾害预警与防护广东省重点实验室
2024年5月20日
