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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

32卷

期数:

2026年01期

页码:

54-60

栏目:

基础医学

出版日期:

2026-01-20

文章信息/Info

Title:

Hyperlipidemia modulates CD177+ neutrophil function to promote hepatic ischemia-reperfusion injury

文章编号:

1006-8147(2026)01-0054-07

作者:

张雨婷; 吕军强; 姚智

（天津医科大学基础医学院免疫学系，天津 300070）

Author(s):

ZHANG Yuting;  Lyu Junqiang;  YAO Zhi

（Department of Immunology， School of Basic Medical Science， Tianjin Medical University， Tianjin 300070， China）

关键词:

高血脂; 肝脏缺血再灌注损伤; 中性粒细胞; 中性粒细胞外捕网

Keywords:

hyperlipidemia;  hepatic ischemia-reperfusion injury;  neutrophils;  neutrophil extracellular traps

分类号:

R392.12

DOI:

10.20135/j.issn.1006-8147.2026.01.0054

文献标志码:

A

摘要:

目的：探讨高血脂加剧肝脏缺血-再灌注损伤（IRI）的免疫应答机制。方法：18只C57BL/6J小鼠用于构建高血脂模型，并进一步构建肝脏缺血-再灌注损伤模型，随机数字表法将其分为Sham组、IRI组和HFD+IRI组（每组6只）。采用HE染色评估肝脏损伤程度，流式细胞术评估肝脏中性粒细胞浸润水平及CD177蛋白表达水平，免疫组织化学分析法评估肝脏CD177+中性粒细胞的浸润水平及PADI4的表达水平。以从正常小鼠骨髓分离的Ly6G+中性粒细胞为研究对象，分为对照组和胆固醇组（40 μmol/L）。胆固醇组采用胆固醇对分离的中性粒细胞进行6 h刺激，实时PCR评估CD177、PADI4和髓过氧化物酶mRNA表达水平。结果：HE染色结果显示，与IRI组相比，HFD+IRI组肝脏损伤程度显著增加（Mean diff=-3.000，P=0.014 9）。流式细胞术结果显示，与IRI组相比，HFD+IRI组肝脏中浸润的Ly6G+CD177+细胞比例显著升高（Mean diff=-17.13，P=0.002 1），CD45+细胞和Ly6G+中性粒细胞中CD177的平均荧光强度（MFI）显著增加（Mean diff=-376.5，P=0.0072；Mean diff=-444.5，P=0.043）。免疫组化结果显示，与IRI组相比，HFD+IRI组肝脏中浸润的CD177+细胞比例显著升高（Mean diff=-113.0，P<0.000 1），PADI4+细胞的数量也进一步提升（Mean diff=-82.8，P<0.000 1）。体外实验结果显示，与对照组相比，胆固醇组Ly6G+中性粒细胞中CD177（t=4.974，P=0.007 6）、PADI4（t=5.963，P=0.004）和MPO（t=7.798，P=0.004 4）mRNA水平显著上调。结论：高脂血症可通过促进CD177+中性粒细胞的肝脏浸润能力，并增强其外捕网形成功能，进而加剧肝脏损伤。

Abstract:

Objective： To investigate the immune response mechanism by which hyperlipidemia exacerbates hepatic ischemia-reperfusion injury （IRI）. Methods： A total of 18 C57BL/6J mice were used to construct a hyperlipidemia model and further construct a hepatic ischemia-reperfusion injury model， which were randomly divided into the Sham group， the IRI group， and the HFD+IRI group（n=6 mice/group）. HE staining was used to assess liver injury. Flow cytometry was used to evaluate neutrophil infiltration in the liver and the expression level of CD177 in neutrophils. Furthermore， immunohistochemical analysis was used to assess CD177+ neutrophils infiltration in the liver and the expression level of PADI4. Ly6G+ neutrophils isolated from the bone marrow of normal mice were used as study subjects and divided into control group and cholesterol group （40 μmol/L）. In the cholesterol group， isolated neutrophils were stimulated with cholesterol for 6 h. Real-time PCR was performed to assess the expression of CD177， PADI4 and MPO mRNA. Results： HE results showed that， compared to the IRI group， liver injury was significantly increased in the HFD+IRI group（Mean diff=-3.000， P=0.014 9）. Flow cytometry results showed that the proportion of infiltrating Ly6G+CD177+ cells in the liver was significantly elevated in the HFD+IRI group compared to the IRI group（Mean diff=-17.13， P=0.002 1）. The mean fluorescence intensity （MFI） of CD177 in CD45+ cells and Ly6G+ neutrophils in the liver were also significantly increased in the HFD+IRI group（CD45+ MFI： Mean diff=-376.5， P=0.007 2； Ly6G+ MFI： Mean diff=-444.5，P=0.043）. Immunohistochemical results showed that the proportion of infiltrating CD177+ cells in the liver was significantly increased in the HFD+IRI group compared to the IRI group （Mean diff= -113.0， P<0.000 1）. The number of PADI4+ cells was also further increased in the HFD+IRI group compared to the IRI group （Mean diff=-82.8， P<0.000 1）. In vitro experimental results showed that， compared to the control group， the mRNA expression of CD177 （t=4.974， P=0.007 6）， PADI4 （t=5.963， P=0.004） and MPO（t=7.798，P=0.004 4） were significantly up-regulated in Ly6G+ neutrophils in the cholesterol group. Conclusion： Hyperlipidemia exacerbates liver injury by promoting the hepatic infiltration of CD177+ neutrophils and enhancing their neutrophil extracellular traps formation function.

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相似文献/References:

备注/Memo

备注/Memo:

基金项目:国家自然科学基金（82241220）
作者简介:张雨婷（2001-），女，硕士在读，研究方向：免疫学；
通信作者:姚智，E-mail：yaozhi@tmu.edu.cn。

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更新日期/Last Update: 2026-01-15