中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (2): 430-440.doi: 10.12307/2025.273

• 组织构建综述 tissue construction review • 上一篇    

巨噬细胞的胞葬作用:肥胖相关代谢性疾病治疗的新靶向

杨风英1,赵玉晴1,油惠娟1,张鹏翼1,陈  岩1,王清路1,刘莹莹2   

  1. 1山东体育学院运动与健康学院,山东省济南市  250102;2空军特色医学中心航天医学研究中心,北京市  100142


  • 收稿日期:2024-01-10 接受日期:2024-03-02 出版日期:2025-01-18 发布日期:2024-05-27
  • 通讯作者: 刘莹莹,空军特色医学中心航天医学研究中心,北京市 100142
  • 作者简介:杨风英,女,1979年生,山东体育学院运动与健康学院引进人才,医学博士,主要从事慢病防治机制研究。
  • 基金资助:
    山东省自然科学基金面上项目(ZR2022MH163),项目负责人:杨风英

Macrophage efferocytosis: a new target for the treatment of obesity-related metabolic diseases #br#
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Yang Fengying1, Zhao Yuqing1, You Huijuan1, Zhang Pengyi1, Chen Yan1, Wang Qinglu1, Liu Yingying2    

  1. 1College of Sports and Health, Shandong Sport University, Jinan 250102, Shandong Province, China; 2Research Center of Aerospace Medicine, Air Force Specialized Medical Center of PLA, Beijing 100142, China
  • Received:2024-01-10 Accepted:2024-03-02 Online:2025-01-18 Published:2024-05-27
  • Contact: Liu Yingying, Research Center of Aerospace Medicine, Air Force Specialized Medical Center of PLA, Beijing 100142, China
  • About author:Yang Fengying, MD, College of Sports and Health, Shandong Sport University, Jinan 250102, Shandong Province, China
  • Supported by:
    Shandong Provincial Natural Science Foundation, No. ZR2022MH163 (to YFY)

摘要:

文题释义:
胞葬作用(efferocytosis):是指吞噬细胞清除凋亡细胞的过程。人体每天有数亿个细胞发生凋亡,凋亡细胞必须被快速地清除以免发生继发性坏死进而释放细胞毒性物质触发炎性损伤。在参与胞葬作用的吞噬细胞中,巨噬细胞发挥胞葬作用的效果最为明显。经过胞葬作用的巨噬细胞由促炎性M1型转化为抗炎性M2型,并释放抗炎因子。因此,通过胞葬作用,一方面清除凋亡细胞,另一方面实现巨噬细胞由促炎型向抗炎型的转化,共同维持机体炎症稳态。
肥胖相关代谢性疾病:肥胖自身是一种由于体内脂肪堆积过多和(或)分布异常引起的慢性代谢性疾病。肥胖将诱发糖尿病、心脑血管疾病、骨关节疾病、神经退行性疾病以及癌症等一系列代谢相关疾病。近年来肥胖相关代谢性疾病发病率不断攀升,已成为严峻的全球公共健康问题。

背景:巨噬细胞胞葬作用障碍引起的局部和系统炎症损害与多种肥胖相关代谢性疾病有关,且以胞葬作用为靶向的化合物表现出良好的治疗效果。
目的:通过综述肥胖对巨噬细胞胞葬作用各个阶段的影响结果分析肥胖抑制胞葬作用的关键机制,总结以胞葬作用为靶向的化合物治疗代谢性疾病的研究现状,以进一步阐明胞葬作用及其与肥胖相关代谢性疾病的关系,为疾病防治策略提供新思路。
方法:以“efferocytosis,metabolism,obesity,obese,atherosclerosis,non-alcoholic steatohepatitis,neurodegeneration,tumor,osteoarthritis,diabetes,compound,medicine,treatment”为英文检索词在PubMed和Web of Science数据库检索英文文献,以“胞葬作用”为中文检索词,在中国知网、万方和维普数据库检索中文文献。经严格筛选最终纳入99篇文献进入综述分析。
结果与结论:①参与巨噬细胞胞葬作用“寻我”“食我”过程的因子中含有大量凋亡细胞源性因子,因此“寻我”“食我”过程主要受凋亡细胞调控;参与骨架重组和消化过程的胞葬因子主要来源于巨噬细胞,对巨噬细胞胞葬作用活性具有决定性作用。此结果提示,“寻我”“食我”过程的因子表达水平主要反映细胞凋亡情况,在评价巨噬细胞胞葬作用活性时,选择骨架重组和消化阶段的胞葬因子的表达更具科学性。②肥胖抑制巨噬细胞胞葬作用,但肥胖对多数“寻我”“食我”因子及骨架重组因子具有应激性激活作用,对多数消化因子具有抑制作用。此结果进一步说明,消化阶段对胞葬作用活性的决定性意义,并提示部分研究以“寻我”“食我”胞葬因子表达增加作为胞葬作用增强的依据不可靠;且提示未来在探讨以巨噬细胞胞葬作用为靶向的干预策略时,靶向消化阶段胞葬因子可能更有效。③巨噬细胞胞葬作用激活物对多种代谢性疾病治疗有效,但肿瘤组织巨噬细胞胞葬作用抑制物表现出良好的抗癌效果,说明应根据组织炎症特点合理评价胞葬作用的意义。④胞葬作用是2003年提出的一个较新概念,研究历程较短,胞葬因子复杂,目前关于肥胖对胞葬作用影响的研究仅涉及冰山一角并且大部分处于粗浅水平,对其更深入的机制探讨仍需大量科学实验的进一步验证。
https://orcid.org/0009-0008-2522-9617(杨风英);https://orcid.org/0009-0006-5903-0900(刘莹莹)
中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

关键词: 肥胖, 巨噬细胞, 胞葬作用, 胞葬因子, 炎症, 代谢性疾病, 化合物, 治疗

Abstract: BACKGROUND: Dysfunction of macrophage efferocytosis can induce local and systemic inflammatory damage and is associated with a variety of obesity-related metabolic diseases. Moreover, compounds targeting efferocytosis have shown good therapeutic effects.
OBJECTIVE: By reviewing the effects of obesity on macrophage efferocytosis, to analyze the key mechanism by which obesity inhibits efferocytosis, to summarize the research progress in compounds targeting efferocytosis to treat obesity-related metabolic diseases, so as to provide new ideas for fully understanding efferocytosis and its relationship with metabolic diseases, aiming to provide new strategies for disease prevention and treatment.
METHODS: The English search terms were “efferocytosis, metabolism, obesity, obese, atherosclerosis, non-alcoholic steatohepatitis, neurodegeneration, tumor, osteoarthritis, diabetes, compound, medicine, treatment,” which were used for literature retrieval in PubMed and Web of Science. The Chinese search term was “efferocytosis,” which was used for literature retrieval in CNKI, VIP and WanFang datebases. Ninety-nine papers were finally included in the review analysis after a rigorous screening process.
RESULTS AND CONCLUSION: In the process of efferocytosis, the “Find me” and “Eat me” processes involving a large number of apoptotic cell derived factors are mainly regulated by apoptotic cells. The efferocytosis factor involved in cytoskeletal remodeling and digestion are mainly derived from macrophages, which are crucial for efferocytosis activity. These results suggest that the “Find me” and “Eat me” factors mainly reflect the condition of apoptosis, and it is more scientific to select the expression of factors involved in cytoskeletal remodeling and digestion when evaluating the efferocytosis activity of macrophages. Obesity inhibits efferocytosis, and shows an inhibitory effect on most digestive factors, but has a stress-induced activation effect on most “Find me,” “Eat me” and cytoskeletal recombination factors, which further indicates the decisive effect of digestive stage on efferocytosis and suggests that it is not reliable for some studies to evaluate the efferocytosis based on the increased expression of “Find me” and “Eat me” factors. Targeting cytokines in the digestive phase may be more effective when discussing future intervention strategies targeting macrophages efferocytosis. The efferocytosis activators of macrophages are effective in the treatment of various metabolic diseases, but the efferocytosis inhibitors in tumor tissue show good anticancer effects, suggesting that the role of efferocytosis should be rationally evaluated according to the characteristics of tissue inflammation. Efferocytosis is a relatively new concept proposed in 2003, with a short research history and complex efferocytosis factors. Current studies on obesity and efferocytosis only involve a tip of the iceberg and most of them are at a superficial level and a large number of scientific experiments are needed to further validate the mechanisms.

Key words: obesity, macrophage, efferocytosis, efferocytosis factor, inflammation, metabolic disease, compound, treatment

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