磷脂酰乙醇胺引起内质网应激促进巨噬细胞衰老及肝损伤

doi:10.3969/j.issn.1674-8115.2025.06.004

上海交通大学学报（医学版） ›› 2025, Vol. 45 ›› Issue (6): 693-704.doi: 10.3969/j.issn.1674-8115.2025.06.004

磷脂酰乙醇胺引起内质网应激促进巨噬细胞衰老及肝损伤

韩龙传¹^,², 李悦¹^,², 邹智慧¹^,², 罗静¹^,²^,³, 李若伊¹, 张颖婷¹^,²^,⁴, 唐欣欣¹^,², 田丽红¹^,²^,³, 陆宇恒¹^,², 黄莺¹, 贺明¹^,²(), 付寅坤¹^,²()

^1.上海交通大学基础医学院病理生理学系，细胞分化与凋亡教育部重点实验室，上海市细胞稳态调控与疾病前沿科学研究基地，上海 200025
^2.上海交通大学医学院附属第九人民医院细胞命运与疾病转化医学研究院，上海 200025
^3.昆明医科大学基础医学院病理学与病理生理学系，昆明 650500
^4.上海交通大学医学院附属瑞金医院中心实验室，上海 200025

收稿日期:2025-01-24 接受日期:2025-02-28 出版日期:2025-06-28 发布日期:2025-06-28
通讯作者: 付寅坤，实验师，博士；电子信箱：yinkunfu@shsmu.edu.cn
贺明，教授，博士；电子信箱：heming@shsmu.edu.cn。
作者简介:韩龙传（1999—），男，硕士生；电子信箱：lc.han@sjtu.edu.cn。
基金资助:
国家自然科学基金(32371244);东方英才计划;上海交通大学医学院高水平地方高校创新团队(SHSMU-ZDCX20212000);上海交通大学医学院基础医学院青年人才支持计划(2024RCZC-C-03)

Phosphatidylethanolamine promotes macrophage senescence and liver injury by activating endoplasmic reticulum stress

HAN Longchuan¹^,², LI Yue¹^,², ZOU Zhihui¹^,², LUO Jing¹^,²^,³, LI Ruoyi¹, ZHANG Yingting¹^,²^,⁴, TANG Xinxin¹^,², TIAN Lihong¹^,²^,³, LU Yuheng¹^,², HUANG Ying¹, HE Ming¹^,²(), FU Yinkun¹^,²()

^1.Frontier Research Center for Cell Homeostasis and Disease Control; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education; Department of Pathophysiology, Shanghai Jiao Tong University College of Basic Medical Sciences, Shanghai 200025, China
^2.Institute for Translational Medicine on Cell Fate and Disease, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
^3.Department of Pathology and Pathophysiology, School of Basic Medicine, Kunming Medical University, Kunming 650500, China
^4.Central Laboratory, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Received:2025-01-24 Accepted:2025-02-28 Online:2025-06-28 Published:2025-06-28
Contact: FU Yinkun, E-mail: yinkunfu@shsmu.edu.cn
HE Ming, E-mail: heming@shsmu.edu.cn.
Supported by:
National Natural Science Foundation of China(32371244);Eastern Talent Plan Leading Project;Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20212000);Youth Talent Support Program Project of the School of Basic Medical Sciences, Shanghai Jiao Tong University School of Medicine(2024RCZC-C-03)

摘要/Abstract

摘要：

目的·探讨磷脂酰乙醇胺（phosphatidylethanolamine，PE）对巨噬细胞衰老及其衰老相关分泌表型的影响和分子机制，以及PE在肝损伤中的病理生理学意义。方法·利用阿霉素建立巨噬细胞衰老模型，并给予PE处理。通过腹腔联合注射PE和脂多糖构建小鼠肝损伤模型，观察PE对肝损伤的影响。采用衰老相关β-半乳糖苷酶（senescence-associated β- galactosidase，SA-β-gal）染色，结合实时荧光定量PCR、Western blotting等检测细胞周期抑制蛋白p21、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）和白介素-6（interleukin-6，IL-6）等衰老标志物及衰老相关分泌表型生物活性因子的表达水平。通过RNA测序结合基因本体论（Gene Ontology，GO）细胞组分富集分析、京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集分析、基因集变异分析（Gene Set Variation Analysis，GSVA）和基因集富集分析（Gene Set Enrichment Analysis，GSEA）筛选PE促进巨噬细胞衰老的信号通路及分子机制。通过体内和体外实验检测内质网应激相关通路中肌醇需求酶1α（inositol requiring enzyme 1 α，IRE1α）、剪接型X盒结合蛋白1（spliced X box binding protein 1，XBP1s）、转录激活因子6（activating transcription factor 6，ATF6）、ATF4、C/EBP同源蛋白（C/EBP homologous protein，CHOP）的表达。结果·PE显著促进巨噬细胞衰老标志物SA-β-gal、p21、p16及衰老相关分泌表型生物活性因子的表达。RNA测序分析显示内质网应激参与PE促进衰老相关分泌表型表达的作用。进一步的实验表明，PE通过激活巨噬细胞内质网应激信号通路促进巨噬细胞衰老及衰老相关分泌表型表达。体内实验证实PE通过内质网应激加剧脂多糖诱导的小鼠肝损伤。结论·PE通过激活内质网应激信号通路，促进巨噬细胞衰老及衰老相关分泌表型生物活性因子分泌，进而加重脂多糖诱导的肝损伤。

关键词: 磷脂酰乙醇胺, 巨噬细胞, 衰老相关分泌表型, 肝损伤, 内质网应激

Abstract:

Objective ·To investigate the effects and molecular mechanisms of phosphatidylethanolamine (PE) on macrophage senescence and its senescence-associated secretory phenotype (SASP), as well as its pathophysiological role in liver injury. Methods ·A macrophage senescence model was established using doxorubicin (DOX), followed by PE treatment. A mouse liver injury model was generated via intraperitoneal co-administration of PE and lipopolysaccharide (LPS) to investigate the effects of PE on liver injury. Senescence markers and SASP factors, including senescence-associated β-galactosidase (SA-β-gal), cell cycle inhibitor p21, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were evaluated using SA-β-gal staining, quantitative real-time PCR, and Western blotting. RNA sequencing (RNA-seq) was performed, followed by Gene Ontology (GO) cellular component enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Gene Set Variation Analysis (GSVA), and Gene Set Enrichment Analysis (GSEA), to explore the molecular mechanisms and signaling pathways by which PE promotes macrophage senescence. The expression of endoplasmic reticulum (ER) stress-related proteins, including inositol-requiring enzyme 1 α (IRE1α), spliced X-box binding protein 1 (XBP1s), activating transcription factor 6 (ATF6), ATF4, and C/EBP homologous protein (CHOP), was analyzed through in vivo and in vitro experiments. Results ·PE significantly promoted the expression of senescence markers SA-β-gal, p21, p16 and SASP factors. RNA-seq analysis revealed that ER stress was involved in PE-induced promotion of SASP. Further experiments demonstrated that PE activated the ER stress signaling pathway, promoting macrophage senescence and the expression of SASP factors. In vivo experiments further confirmed that PE exacerbated LPS-induced liver injury in mice through ER stress. Conclusion ·PE promotes macrophage senescence and the expression of SASP factors by activating ER stress signaling pathway, thereby aggravating LPS-induced liver injury.

Key words: phosphatidylethanolamine (PE), macrophage, senescence-associated secretory phenotype (SASP), liver injury, endoplasmic reticulum stress

中图分类号:

Q255

韩龙传, 李悦, 邹智慧, 罗静, 李若伊, 张颖婷, 唐欣欣, 田丽红, 陆宇恒, 黄莺, 贺明, 付寅坤. 磷脂酰乙醇胺引起内质网应激促进巨噬细胞衰老及肝损伤[J]. 上海交通大学学报（医学版）, 2025, 45(6): 693-704.

HAN Longchuan, LI Yue, ZOU Zhihui, LUO Jing, LI Ruoyi, ZHANG Yingting, TANG Xinxin, TIAN Lihong, LU Yuheng, HUANG Ying, HE Ming, FU Yinkun. Phosphatidylethanolamine promotes macrophage senescence and liver injury by activating endoplasmic reticulum stress[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(6): 693-704.

图/表 6

表1 实时荧光定量PCR的引物序列

Tab 1 Primer sequences for quantitative real-time PCR

Gene	Forward primer (5′→3′)	Reverse primer (5′→3′)
p21	CCTGGTGATGTCCGACCTG	CCATGAGCGCATCGCAATC
p16	CCAGGGCCGTGTGCAT	TACGTGAACGTTGCCCATCA
Tnf-α	GCCACCACGCTCTTCTGTCTAC	GGGTCTGGGCCATAGAACTGAT
Il-6	GTTGTGCAATGGCAATTCTG	CTGGCTTTGTCTTTCTTGTTATCT
Il-1β	GCAACTGTTCCTGAACTCAACT	ATCTTTTGGGGTCCGTCAACT
Cxcl1	CTGCACCCAAACCGAAGTC	CCAGGGCCGTGTGCAT
Mmp13	CTTCTTCTTGTTGAGCTGGACTC	CTGTGGAGGTCACTGTAGACT
Ire1α	TCCTAACAACCTGCCCAAACA	AGATACGGTGGTCGGTGTGT
Atf6	GCAATACCTGTTCTTCCTCTGA	TCTAAACACCCACAAGCCACA
Chop	CCACCACACCTGAAAGCAGAA	AGGTGAAAGGCAGGGACTCA
β-actin	GGCTGTATTCCCCTCCATCG	CCAGTTGGTAACAATGCCATGT

图1 PE促进巨噬细胞衰老及衰老相关分泌表型表达Note： A. Representative images of SA-β-gal staining in RAW264.7 cells treated with different concentrations of PE (0, 10, 50 and 125 μmol·L-1) in the presence or absence of DOX (0.5 μmol·L-1), bar=50 μm. B/C. Quantitative real-time PCR analysis of expression of senescence markers p21 (B) and p16 (C) in RAW264.7 cells treated with different concentrations of PE (0, 10, 50 and 125 μmol·L-1) in the presence of DOX. D. Western blotting analysis of senescence markers. E‒I. Quantitative real-time PCR analysis of expression of senescence-associated secretory phenotype (SASP) factors Tnf-α (E), Il-6 (F), Il-1β (G), Cxcl1 (H) and Mmp13 (I). ①P<0.001, ②P=0.001, ③P=0.021, ④P=0.005, ⑤P=0.027, ⑥P=0.023, ⑦P=0.031, ⑧P=0.019, ⑨P=0.009, ⑩P=0.045, ⑪P=0.008, ⑫P=0.002. DOX—doxorubicin.

Fig 1 PE promotes cellular senescence and the expression of SASP in macrophages

图2 PE处理的衰老巨噬细胞RNA测序功能富集分析Note： The DOX group was treated with 0.5 μmol·L-1 DOX, while the PE group was treated with 50 μmol·L-1 PE in combination with DOX. A. GO enrichment analysis of cellular component categories, presented as an enrichment factor plot [(PE+DOX) vs DOX]. B. KEGG pathway enrichment analysis displayed as an enrichment factor plot [(PE+DOX) vs DOX]. C. Heatmap of GSVA [(PE+DOX) vs DOX]. D. GSEA of endoplasmic reticulum unfolded protein response and response to endoplasmic reticulum stress [(PE+DOX) vs DOX].

Fig 2 Functional enrichment analysis of RNA sequencing data from senescent macrophages treated with PE

图3 PE通过引起内质网应激信号通路促进巨噬细胞衰老和衰老相关分泌表型表达Note：A‒C. Quantitative real-time PCR analysis of Ire1α (A), Atf6 (B) and Chop (C) mRNA expression in RAW264.7 cells treated with DOX and PE (50 μmol·L-1). D. Western blotting analysis of endoplasmic reticulum stress-related proteins, including p-IRE1α, IRE1α, ATF6-P, ATF6-N, XBP1s and ATF4. E. SA-β-gal staining of RAW264.7 cells treated with Toyocamycin, DOX and PE. F/G. Quantitative real-time PCR analysis of senescence marker mRNA expression, including p21 (F) and p16 (G). H. Western blotting analysis of proteins including p21 and p16. I‒M. Quantitative real-time PCR analysis of SASP mRNA expression, including Tnf-α (I), Il-6 (J), Il-1β (K), Cxcl1 (L) and Mmp13 (M). ①P=0.033, ②P=0.009, ③P<0.001, ④P=0.014, ⑤P=0.012, ⑥P=0.005, ⑦P=0.003, ⑧P=0.008, ⑨P=0.010.

Fig 3 PE promotes macrophage senescence and SASP through activating endoplasmic reticulum stress signaling pathway

图4 PE加剧脂多糖诱导的肝损伤Note： Mice were divided into the PE group, lipopolysaccharide (LPS) group, and PE+LPS group by intraperitoneal injection of PE, LPS, and PE combined with LPS, respectively, with an additional blank control (CTRL) group. A. General morphology, HE staining and immunohistochemistry of the liver from the four groups of mice. HE staining, bar=100 μm; SA-β-gal immunohistochemistry, bar=200 μm; p21 immunohistochemistry, bar=100 μm. Red arrows indicate p21-positive cells. B. Percentages of liver weight. C. Plasma AST in the indicated mice. D. TUNEL staining of liver, bar=50 μm. Red arrows indicate TUNEL-positive cells. ①P<0.001, ②P=0.041, ③P=0.037.

Fig 4 PE exacerbates lipopolysaccharide-induced liver injury

图5 PE促进肝脏内质网应激、细胞衰老及衰老相关分泌表型基因表达Note： A. Western blotting analysis of liver lysates from the control (CTRL), PE, LPS, and PE+LPS groups. B‒H. Quantitative real-time PCR analysis of senescence markers and SASP mRNA expression in mouse liver, including p21 (B), p16 (C), Tnf-α (D), Il-6 (E), Il-1β (F), Cxcl1 (G)and Mmp13 (H). ①P=0.019, ②P=0.024, ③P=0.046, ④P=0.002, ⑤P=0.010, ⑥P=0.014, ⑦P=0.003, ⑧P=0.006, ⑨P=0.007, ⑩P=0.008, ⑪P=0.018.

Fig 5 PE promotes the expression of endoplasmic reticulum stress, cellular senescence, and SASP-related genes in the liver

参考文献 31

[1]	LÓPEZ-OTÍN C, BLASCO M A, PARTRIDGE L, et al. Hallmarks of aging: an expanding universe[J]. Cell, 2023, 186(2): 243-278.
[2]	ZHANG L, PITCHER L E, YOUSEFZADEH M J, et al. Cellular senescence: a key therapeutic target in aging and diseases[J]. J Clin Invest, 2022, 132(15): e158450.
[3]	GUO J, HUANG X Q, DOU L, et al. Aging and aging-related diseases: from molecular mechanisms to interventions and treatments[J]. Signal Transduct Target Ther, 2022, 7(1): 391.
[4]	SWEET M J, RAMNATH D, SINGHAL A, et al. Inducible antibacterial responses in macrophages[J]. Nat Rev Immunol, 2025, 25: 92-107.
[5]	PEISELER M, DAVID B A, ZINDEL J, et al. Kupffer cell-like syncytia replenish resident macrophage function in the fibrotic liver[J]. Science, 2023, 381(6662): eabq5202.
[6]	WANG L L, HONG W X, ZHU H, et al. Macrophage senescence in health and diseases[J]. Acta Pharm Sin B, 2024, 14(4): 1508-1524.
[7]	LIU Z Q, LIANG Q M, REN Y Q, et al. Immunosenescence: molecular mechanisms and diseases[J]. Signal Transduct Target Ther, 2023, 8(1): 200.
[8]	ZHAO B H, WU B, FENG N, et al. Aging microenvironment and antitumor immunity for geriatric oncology: the landscape and future implications[J]. J Hematol Oncol, 2023, 16(1): 28.
[9]	BIRCH J, GIL J. Senescence and the SASP: many therapeutic avenues[J]. Genes Dev, 2020, 34(23/24): 1565-1576.
[10]	LEON K E, BUJ R, LESKO E, et al. DOT1L modulates the senescence-associated secretory phenotype through epigenetic regulation of IL1A[J]. J Cell Biol, 2021, 220(8): e202008101.
[11]	WANG B S, HAN J, ELISSEEFF J H, et al. The senescence-associated secretory phenotype and its physiological and pathological implications[J]. Nat Rev Mol Cell Biol, 2024, 25(12): 958-978.
[12]	ROH K, NOH J, KIM Y, et al. Lysosomal control of senescence and inflammation through cholesterol partitioning[J]. Nat Metab, 2023, 5(3): 398-413.
[13]	YOSHIMOTO S, LOO T M, ATARASHI K, et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome[J]. Nature, 2013, 499(7456): 97-101.
[14]	LIU X, HARTMAN C L, LI L Y, et al. Reprogramming lipid metabolism prevents effector T cell senescence and enhances tumor immunotherapy[J]. Sci Transl Med, 2021, 13(587): eaaz6314.
[15]	GIBELLINI F, SMITH T K. The Kennedy pathway: de novo synthesis of phosphatidylethanolamine and phosphatidylcholine[J]. IUBMB Life, 2010, 62(6): 414-428.
[16]	PATEL D, WITT S N. Ethanolamine and phosphatidylethanolamine: partners in health and disease[J]. Oxid Med Cell Longev, 2017, 2017: 4829180.
[17]	TACIAK B, BIAŁASEK M, BRANIEWSKA A, et al. Evaluation of phenotypic and functional stability of RAW 264.7 cell line through serial passages[J]. PLoS One, 2018, 13(6): e0198943.
[18]	FACCHIN B M, DOS REIS G O, VIEIRA G N, et al. Inflammatory biomarkers on an LPS-induced RAW 264.7 cell model: a systematic review and meta-analysis[J]. Inflamm Res, 2022, 71(7/8): 741-758.
[19]	YEN L, SVENDSEN J, LEE J S, et al. Exogenous control of mammalian gene expression through modulation of RNA self-cleavage[J]. Nature, 2004, 431(7007): 471-476.
[20]	EL MANAA W, DUPLAN E, GOIRAN T, et al. Transcription- and phosphorylation-dependent control of a functional interplay between XBP1s and PINK1 governs mitophagy and potentially impacts Parkinson disease pathophysiology[J]. Autophagy, 2021, 17(12): 4363-4385.
[21]	ZHANG G Z, ZHAN M S, ZHANG C C, et al. Redox-responsive dendrimer nanogels enable ultrasound-enhanced chemoimmunotherapy of pancreatic cancer via endoplasmic reticulum stress amplification and macrophage polarization[J]. Adv Sci (Weinh), 2023, 10(24): e2301759.
[22]	XUE L J, LIU K, YAN C X, et al. Schisandra lignans ameliorate nonalcoholic steatohepatitis by regulating aberrant metabolism of phosphatidylethanolamines[J]. Acta Pharm Sin B, 2023, 13(8): 3545-3560.
[23]	TIGHANIMINE K, NABUCO LEVA FERREIRA FREITAS J A, NEMAZANYY I, et al. A homoeostatic switch causing glycerol-3-phosphate and phosphoethanolamine accumulation triggers senescence by rewiring lipid metabolism[J]. Nat Metab, 2024, 6(2): 323-342.
[24]	ZHANG L Z, RICHARD A S, JACKSON C B, et al. Phosphatidylethanolamine and phosphatidylserine synergize to enhance GAS6/AXL-mediated virus infection and efferocytosis[J]. J Virol, 2020, 95(2): e02079-20.
[25]	VAZQUEZ-DE-LARA L G, TLATELPA-ROMERO B, ROMERO Y, et al. Phosphatidylethanolamine induces an antifibrotic phenotype in normal human lung fibroblasts and ameliorates bleomycin-induced lung fibrosis in mice[J]. Int J Mol Sci, 2018, 19(9): 2758.
[26]	HUANG F Z, LIU X M, LIU J J, et al. Phosphatidylethanolamine aggravates Angiotensin Ⅱ-induced atrial fibrosis by triggering ferroptosis in mice[J]. Front Pharmacol, 2023, 14: 1148410.
[27]	LI L, CUI L, LIN P, et al. Kupffer-cell-derived IL-6 is repurposed for hepatocyte dedifferentiation via activating progenitor genes from injury-specific enhancers[J]. Cell Stem Cell, 2023, 30(3): 283-299.e9.
[28]	FANG P P, XIANG L X, HUANG S S, et al. IRE1α-XBP1 signaling pathway regulates IL-6 expression and promotes progression of hepatocellular carcinoma[J]. Oncol Lett, 2018, 16(4): 4729-4736.
[29]	RI M, TASHIRO E, OIKAWA D, et al. Identification of Toyocamycin, an agent cytotoxic for multiple myeloma cells, as a potent inhibitor of ER stress-induced XBP1 mRNA splicing[J]. Blood Cancer J, 2012, 2(7): e79.
[30]	SONG N, SONG Y Q, HU B B, et al. Persistent endoplasmic reticulum stress stimulated by peptide assemblies for sensitizing cancer chemotherapy[J]. Adv Healthcare Mater, 2023, 12(5): 2202039.
[31]	YIN N, ZHANG W J, SUN X X, et al. Artificial cells delivering itaconic acid induce anti-inflammatory memory-like macrophages to reverse acute liver failure and prevent reinjury[J]. Cell Rep Med, 2023, 4(8): 101132.

磷脂酰乙醇胺引起内质网应激促进巨噬细胞衰老及肝损伤

Phosphatidylethanolamine promotes macrophage senescence and liver injury by activating endoplasmic reticulum stress

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 6

参考文献 31

相关文章 15

编辑推荐

Metrics

[1]	姜芊羽, 姚程程, 季萍, 王颖. HAMA水凝胶促进皮肤创面愈合的组织局部微环境特征[J]. 上海交通大学学报（医学版）, 2025, 45(8): 969-980.
[2]	王琳, 徐萍, 张乔婷, 田军, 娄晓丽, 王静. 胱天蛋白酶募集域蛋白9在重症急性胰腺炎巨噬细胞M1极化中的作用[J]. 上海交通大学学报（医学版）, 2025, 45(8): 981-989.
[3]	杨乐, 周怡, 王钶韵, 赖娅莉. 大黄素改善阿尔茨海默病认知障碍、内质网应激和神经炎症的研究[J]. 上海交通大学学报（医学版）, 2025, 45(6): 727-734.
[4]	黄英荷, 招冠钰, 孙阳, 侯鉴基, 左勇. 2型糖尿病创面愈合中巨噬细胞代谢调控的研究进展[J]. 上海交通大学学报（医学版）, 2025, 45(6): 792-799.
[5]	汤开然, 冯成领, 韩邦旻. 基于单细胞测序与转录组测序构建M2巨噬细胞基因相关的前列腺癌预后模型[J]. 上海交通大学学报（医学版）, 2025, 45(5): 549-561.
[6]	徐苓, 皇甫昱婵, 沈立松, 马妍慧. 两样本孟德尔随机化分析血浆磷脂酰乙醇胺水平与结直肠腺癌发病风险的关系[J]. 上海交通大学学报（医学版）, 2025, 45(5): 605-613.
[7]	倪书奕, 姜钊, 汪中涛, 何树梅. 红景天苷对卡介苗感染的巨噬细胞免疫功能的影响[J]. 上海交通大学学报（医学版）, 2025, 45(4): 426-433.
[8]	马秀珍, 周妮, 郭思琪, 王源媛, 麦平. 大麻素受体1通过Gα_i/o/RhoA信号通路促进急性肺损伤小鼠巨噬细胞M1极化[J]. 上海交通大学学报（医学版）, 2025, 45(2): 161-168.
[9]	张烨晟, 杨易静, 黄依雯, 施珑玙, 王曼媛, 陈思思. 肿瘤微环境免疫细胞调节肿瘤细胞耐药性的研究进展[J]. 上海交通大学学报（医学版）, 2024, 44(7): 830-838.
[10]	牛媛媛, 汪龙德, 胥文娟, 李正菊, 张瑞婷, 吴毓谦. 巨噬细胞M1/M2型极化在不同肝病中的作用研究进展[J]. 上海交通大学学报（医学版）, 2024, 44(4): 509-517.
[11]	张羽桐, 侯国俊, 沈南. 单细胞基因组学比较人诱导多能干细胞来源巨噬细胞与外周血来源巨噬细胞的异质性[J]. 上海交通大学学报（医学版）, 2024, 44(12): 1477-1489.
[12]	边姝, 于倩, 刘亮明. 内源性大麻素系统在肝脏病中作用的研究进展[J]. 上海交通大学学报（医学版）, 2024, 44(10): 1299-1306.
[13]	贾君杰, 邢海帆, 张群子, 刘奇烨, 汪年松, 范瑛. 缺氧诱导因子-1α抑制剂YC-1改善糖尿病肾病小鼠肾脏损伤的机制研究[J]. 上海交通大学学报（医学版）, 2023, 43(9): 1089-1098.
[14]	宋文汀, 陶悦, 潘艺, 莫茜, 曹清. SIRT2通过组蛋白H4K8去乳酸化修饰调控巨噬细胞趋化功能[J]. 上海交通大学学报（医学版）, 2023, 43(8): 1008-1016.
[15]	董海平, 谢海怡, 马晓晓, 王震虹. 脑卒中后脑血管内皮细胞内质网应激抑制Wnt7/β-catenin通路导致血脑屏障损伤的机制研究[J]. 上海交通大学学报（医学版）, 2023, 43(7): 829-838.