芝麻素抑制巨噬细胞M1极化改善非酒精性脂肪肝病小鼠肝脏损伤

doi:10.12092/j.issn.1009-2501.2026.06.014

中国临床药理学与治疗学 ›› 2026, Vol. 31 ›› Issue (6): 844-850.doi: 10.12092/j.issn.1009-2501.2026.06.014

• 基础研究 • 上一篇

芝麻素抑制巨噬细胞M1极化改善非酒精性脂肪肝病小鼠肝脏损伤

马军民¹(), 孙玥², 陶燕华¹, 魏蓓¹, 王秋云³^,⁴, 张翠微³^,⁴, 王国栋⁵, 孔祥³^,⁴^,*(), 章浩然⁴^,*()

1. 芜湖市第一人民医院内分泌科，芜湖 241100，安徽
2. 池州市人民医院老年医学科，池州 247000，安徽
3. 皖南医科大学第一附属医院，弋矶山医院，老年医学科，内分泌亚专业，芜湖 241001，安徽
4. 国家老年疾病临床医学研究中心安徽省分中心，芜湖 241001，安徽
5. 皖南医科大学药学院，芜湖 241002，安徽

收稿日期:2025-06-17 出版日期:2026-06-26 发布日期:2026-07-06
通讯作者: 孔祥,章浩然 E-mail:1094847287@qq.com;wnmcyaolikx@sina.com;610180105@qq.com
作者简介:马军民，男，副主任医师，研究方向：糖尿病防治研究。E-mail：1094847287@qq.com
基金资助:
国家自然科学基金（81970699）；安徽省卫生健康科研项目青年项目（AHWJ2023A30185）；安徽省卫生健康科研项目重点项目（AHWJ2024Aa10024）

Sesamin improves liver injury in nonalcoholic fatty liver disease mice by inhibiting M1 macrophage polarization

Junmin MA¹(), Yue SUN², Yanhua TAO¹, Bei WEI¹, Qiuyun WANG³^,⁴, Cuiwei ZHANG³^,⁴, Guodong WANG⁵, Xiang KONG³^,⁴^,*(), Haoran ZHANG⁴^,*()

1. Department of Endocrinology, Wuhu First People's Hospital, Wuhu 241100, Anhui, China
2. Department of Gerontology, Chizhou People's Hospital, Chizhou 247000, Anhui, China
3. Department of Gerontology, Geriatric Endocrinology Unit, The First Affiliated Hospital of Wannan Medical University, Yijishan Hospital,Wuhu241001, Anhui, China
4. National Clinical Research Center for Geriatric Diseases, Anhui Provincial Sub-center, Wuhu 241001, Anhui, China
5. School of Pharmacy, Wannan Medical University, Wuhu 241002, Anhui, China

Received:2025-06-17 Online:2026-06-26 Published:2026-07-06
Contact: Xiang KONG,Haoran ZHANG E-mail:1094847287@qq.com;wnmcyaolikx@sina.com;610180105@qq.com

摘要/Abstract

摘要：

目的: 探讨芝麻素（sesamin，Ses）能否通过抑制巨噬细胞M1极化改善非酒精性脂肪肝病（nonalcoholic fatty liver disease，NAFLD）小鼠肝脏损伤。方法: 应用原代小鼠骨髓源性巨噬细胞（bone marrow-derived macrophages，BMDMs）体外极化模型和高脂饲料喂饲NAFLD小鼠模型，芝麻素治疗后检测BMDMs和小鼠肝脏组织炎症因子水平、M1型巨噬细胞标志物诱导型一氧化氮合酶（inducible nitric oxide synthase，iNOS）表达及磷酸化信号转导与转录激活子1（phosphorylated-signal transducer and activator of transcription 1，P-STAT1）表达；检测小鼠血清肝功能指标；制备肝脏组织切片后行HE染色、F4/80和P-STAT1免疫组化及免疫荧光染色。结果: 芝麻素治疗降低脂多糖处理的BMDMs中IL-1β和IL-6水平（P<0.01）、抑制iNOS和P-STAT1表达（P<0.01）。芝麻素治疗降低NAFLD小鼠体质量，改善肝脏损伤（P<0.01）。芝麻素治疗组小鼠肝脏巨噬细胞数量减少，IL-1β、IL-6含量以及iNOS、P-STAT1表达降低（P<0.01）。结论: 芝麻素改善NAFLD小鼠肝脏损伤，其作用与芝麻素降低STAT1磷酸化，抑制巨噬细胞M1极化有关。

关键词: 芝麻素, 非酒精性脂肪肝病, 巨噬细胞M1极化

Abstract:

AIM: To investigate whether Ses can improve liver injury in nonalcoholic fatty liver disease (NAFLD) mice by inhibiting M1 macrophages polarization. METHODS: A primary mouse bone marrow-derived macrophage (BMDMs) polarization model and a high-fat diet-fed NAFLD mouse model were used. After Ses treatment, the levels of inflammatory factors in BMDMs and mouse liver tissue, the expression of inducible nitric oxide synthase (iNOS, an M1 macrophage marker) and phosphorylated-signal transducer and activator of transcription1 (P-STAT1) were measured. Serum liver function indicators were also tested. Liver tissue sections were prepared for HE staining, F4/80 and P-STAT1 immunohistochemistry and immunofluorescence staining. RESULTS: Ses treatment reduced the levels of IL-1β and IL-6 in LPS-treated BMDMs and inhibited the expression of iNOS and P-STAT1. Ses treatment reduced the body weight of NAFLD mice and improved liver damage (P<0.01). In the Ses treatment group, the number of macrophages in the liver decreased, and the levels of IL-1β and IL-6, as well as the expression of iNOS and P-STAT1, were reduced(P<0.01). CONCLUSIONS: Ses improves liver damage in NAFLD mice. These effects may be associated with reduction of STAT1 phosphorylation and inhibition of M1 macrophage polarization.

Key words: sesamin, nonalcoholic fatty liver disease, M1 macrophage polarization

中图分类号:

R965.2

马军民, 孙玥, 陶燕华, 魏蓓, 王秋云, 张翠微, 王国栋, 孔祥, 章浩然. 芝麻素抑制巨噬细胞M1极化改善非酒精性脂肪肝病小鼠肝脏损伤[J]. 中国临床药理学与治疗学, 2026, 31(6): 844-850.

Junmin MA, Yue SUN, Yanhua TAO, Bei WEI, Qiuyun WANG, Cuiwei ZHANG, Guodong WANG, Xiang KONG, Haoran ZHANG. Sesamin improves liver injury in nonalcoholic fatty liver disease mice by inhibiting M1 macrophage polarization[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(6): 844-850.

图/表 6

图 1

Fig.1 Effects of Ses treatment on the levels of inflammatory factors in BMDMs ($\bar x $±s) BMDMs were treated with 50 or 100 μmol/L Ses for 48 h and then treated with 100 ng/mL LPS for 24 h. A: inflammatory factor chip detection, n=3. The red box and yellow box represent IL-1β and IL-6, respectively. B and C: results of mRNA expression of IL-1β and IL-6, n=3. D and E: supernatant levels of IL-1β and IL-6 were quantified using ELISA assay, n = 3. **P<0.01.

图 2

Fig.2 Effects of Ses treatment on M1 macrophage polarization in BMDMs ($\bar x $±s) BMDMs were treated with 50 or 100 μmol/L Ses for 48 h and then treated with 100 ng/mL LPS for 24 h. A: representative immunofluorescence staining images of the iNOS protein in the BMDMs (scale bar=25 μm). B: results of mRNA expression of iNOS, n=3. C and D: the panel and histogram of iNOS protein expression, n=3. *P<0.05, **P<0.01.

图 3

Fig.3 Effects of Ses treatment on LPS-induced P-STAT1 expression in BMDMs ($\bar x $±s) BMDMs were treated with 50 or 100 μmol/L Ses for 48 h and then treated with 100 ng/mL LPS for 24 h. A-C: the panel and histogram of P-STAT1 Tyr701 and P-STAT1 Ser727 protein expression, n=3. *P<0.05, **P<0.01.

图 4

Fig.4 Effects of Ses treatment on liver injury in NAFLD mice ($\bar x $±s) A: body weight; B: liver weight; C: serum ALT level; D: serum AST level; E: serum TC level; F: serum TG level, n=6. *P<0.05, **P<0.01. G: representative HE staining images of mice liver tissue. The arrow indicates steatosis. (scale bar=100 μm).

图 5

Fig.5 Effects of Ses treatment on liver M1 macrophage polarization in NAFLD mice ($\bar x $±s) A: representative immunohistochemistry staining images of F4/80 in mice liver tissue (scale bar=50 μm). B: the number of F4/80 positive macrophages was calculated, n=3. C: results of mRNA expression of iNOS, n=3. D and E: levels of IL-1β and IL-6 in mice liver tissue were quantified using ELISA assay, n=6. **P<0.01.

图 6

Fig.6 Effects of Ses treatment on liver P-STAT1 expression in NAFLD mice ($\bar x $±s) A-C: the panel and histogram of P-STAT1 Tyr701 and P-STAT1 Ser727 protein expression in mice liver tissue, n=3, **P<0.01. D: representative immunofluorescence staining images of F4/80 and P-STAT1 Ser727 in mice liver tissue (scale bar=50 μm).

参考文献 15

1	Huang DQ, Wong VWS, Rinella ME, et al. Metabolic dysfunction-associated steatotic liver disease in adults[J]. Nat Rev Dis Primers, 2025, 11 (1): 14. doi: 10.1038/s41572-025-00599-1
2	Powell EE, Wong VW, Rinella M. Non-alcoholic fatty liver disease[J]. Lancet, 2021, 397 (10290): 2212- 2224. doi: 10.1016/S0140-6736(20)32511-3
3	Shi L, Karrar E, Liu R, et al. Comparative effects of sesame lignans (sesamin, sesamolin, and sesamol) on oxidative stress and lipid metabolism in steatosis HepG2 cells[J]. J Food Biochem, 2022, 46 (8): e14180. doi: 10.1111/jfbc.14180
4	Bai YP, Zhang T, Hu ZY, et al. Sesamin ameliorates nonalcoholic hepatic steatosis by inhibiting CD36-mediated hepatocyte lipid accumulation in vitro and in vivo[J]. Biochem Pharmacol, 2024, 224, 116240. doi: 10.1016/j.bcp.2024.116240
5	Zhang T, Zhou Y, Zhang Y, et al. Sesamin ameliorates nonalcoholic steatohepatitis through inhibiting hepatocyte pyroptosis in vivo and in vitro[J]. Front Pharmacol, 2024, 15, 1347274. doi: 10.3389/fphar.2024.1347274
6	Cao Y, Mai W, Li R, et al. Macrophages evoke autophagy of hepatic stellate cells to promote liver fibrosis in NAFLD mice via the PGE2/EP4 pathway[J]. Cell Mol Life Sci, 2022, 79 (6): 303. doi: 10.1007/s00018-022-04319-w
7	Phitak T, Pothacharoen P, Settakorn J, et al. Chondroprotective and anti-inflammatory effects of sesamin[J]. Phytochemistry, 2012, 80, 77- 88. doi: 10.1016/j.phytochem.2012.05.016
8	Bai YP, Xing YJ, Ma T, et al. β-Hydroxybutyrate suppresses M1 macrophage polarization through β-hydroxybutyrylation of the STAT1 protein[J]. Cell Death Dis, 2024, 15 (12): 874. doi: 10.1038/s41419-024-07268-3
9	Xing YJ, Zhang T, Wan SJ, et al. LncRNA HEM2ATM improves obesity-associated adipose tissues meta-inflammation and insulin resistance by interacting with heterogeneous nuclear ribonucleoprotein U[J]. Clin Immunol, 2023, 247, 109234. doi: 10.1016/j.clim.2023.109234
10	Orecchioni M, Ghosheh Y, Pramod AB, et al. Macrophage polarization: different gene signatures in M1 (LPS+) vs. classically and M 2(LPS-) vs. alternatively activated macrophages[J]. Front Immunol, 2019, 10, 1084. doi: 10.3389/fimmu.2019.01084
11	Cao J, Ji L, Zhan Y, et al. MST4 kinase regulates immune thrombocytopenia by phosphorylating STAT1-mediated M1 polarization of macrophages[J]. Cell Mol Immunol, 2023, 20, 1413- 1427. doi: 10.1038/s41423-023-01089-8
12	Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders[J]. Nature, 2017, 542 (7640): 177- 185. doi: 10.1038/nature21363
13	Li C, Xu MM, Wang K, et al. Macrophage polarization and meta-inflammation[J]. Transl Res, 2018, 191, 29- 44. doi: 10.1016/j.trsl.2017.10.004
14	Kazankov K, Jørgensen SMD, Thomsen KL, et al. The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[J]. Nat Rev Gastroenterol Hepatol, 2019, 16 (3): 145- 159. doi: 10.1038/s41575-018-0082-x
15	Metwally H, Tanaka T, Li S, et al. Noncanonical STAT1 phosphorylation expands its transcriptional activity into promoting LPS-induced IL-6 and IL-12p40 production[J]. Sci Signal, 2020, 13 (624): 0574. doi: 10.1126/scisignal.aay0574

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芝麻素抑制巨噬细胞M1极化改善非酒精性脂肪肝病小鼠肝脏损伤

Sesamin improves liver injury in nonalcoholic fatty liver disease mice by inhibiting M1 macrophage polarization

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