中华中医药学刊

山楂提取物通过NETs影响T细胞调控血脂异常的作用机制研究

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周碧聪 ¹ , 杨莺 ²

中华中医药学刊 | 国家项目点击 2026,44(3): 55-59

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中华中医药学刊 |国家项目点击 2026 , 44 (3) : 55 -59

山楂提取物通过NETs影响T细胞调控血脂异常的作用机制研究

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周碧聪¹, 杨莺²

作者信息

^1.辽宁中医药大学，辽宁沈阳 110847

^2.辽宁中医药大学附属医院，辽宁沈阳 110032

通讯作者:

杨莺（1976 -），女，辽宁沈阳人，主任医师，博士研究生导师，博士，研究方向：中西医结合防治心血管疾病。E-mail：yy20170225@sina.com。

作者简介:

周碧聪（1997 -），女，甘肃临夏人，硕士在读，研究方向：中西医结合防治心血管疾病。

Mechanism of Shanzha（Hawthorn）Extract in Regulating Dyslipidemia by Affecting T Cells Through NETs

Bicong ZHOU¹, Ying YANG²

Affiliations

^1.Liaoning University of Traditional Chinese Medicine, Shenyang 110847, Liaoning, China

^2.Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, Liaoning, China

出版时间: 2026-03-10 doi: 10.13193/j.issn.1673-7717.2026.03.010

文章导航

摘要

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目的

探讨山楂提取物通过中性粒细胞胞外诱捕网（Neutrophil Extracellular Traps，NETs）影响血脂异常小鼠T细胞的分化并调控血脂水平的作用机制研究。

方法

50只雄性6周龄C57BL/6J小鼠适应性饲养1周后，10只予以普通饲料喂养，40只予以60%高脂饲料喂养建立高脂小鼠模型，造模4周后，将高脂小鼠随机分为高脂饮食组（High Fat Diet，HFD）、HFD +山楂提取物组、HFD + NETs抑制剂载体溶剂组、HFD + NETs抑制剂GSK484组。HFD +山楂提取物组小鼠山楂提取物灌胃，5.2 g/（kg·d），HFD + NETs抑制剂GSK484组腹腔注射GSK484，4 mg/（kg·d），HFD + NETs抑制剂载体溶剂组腹腔注射等量载体溶剂，对照组和HFD组同时间口服等量蒸馏水。给药4周后，生化分析仪检测血清总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇含量；酶联免疫吸附测定技术检测血清干扰素-γ（Interferon-gamma，IFN-γ）、白细胞介素-4（Interleukin-4，IL-4）、白细胞介素-10（Interleukin-10，IL-10）、白细胞介素-17A（Interleukin-17A，IL-17A）、白细胞介素-21（Interleukin-21，IL-21）含量；免疫荧光双染法检测中性粒细胞髓过氧化物酶（Myeloperoxidase，MPO）和瓜氨酸化的组蛋白（Citrullinated histone H3，CitH3）表达分析NETs形成，蛋白免疫印迹法检测外周血单个核细胞T-box转录因子21（T-box Transcription Factor 21，TBx21）、Gata结合蛋白3（GATA-Binding Protein 3，Gata-3）、维甲酸相关孤核受体γt（Retinoic Acid-Related Orphan Nuclear Receptor Gamma γt，RORγt）、叉头样转录因子3（Forkhead Box Protein P3，Foxp3）、B细胞淋巴瘤6（B-cell lymphoma 6，Bcl-6）蛋白表达。

结果

相较于正常对照组，高脂饮食小鼠体质量显著增加，HFD组小鼠TC、TG、LDL-C水平显著升高，HDL-C水平显著降低，IFN-γ、IL-17A、IL-21显著升高，IL-4和IL-10显著降低，MPO、CitH3表达水平显著升高，外周血蛋白Tbx21、RORγt表达量显著增加，Gata3、Foxp3、Bcl-6表达量显著减少。与HDF组相比，HFD +山楂提取物组和HFD + NETs抑制剂GSK484组小鼠体重显著降低，TC、TG、LDL-C水平显著降低，HDL-C显著升高，IFN-γ、IL-17A、IL-21均显著降低，IL-4显著增加，而IL-10相较于HFD组，在HFD +山楂提取物组中表达显著增加，在HFD + NETs抑制剂GSK484组中无显著差异性。与HFD组相比，HFD +山楂提取物组和HFD + NETs抑制剂GSK484组MPO、CitH3表达水平均显著减少，Tbx21、RORγt蛋白表达量均显著降低，Gata3蛋白表达量均显著增加，而Bcl-6和Foxp3在HFD +山楂提取物组中表达显著增高，在HFD + NETs抑制剂GSK484组中显著降低。

结论

山楂提取物通过降低血脂异常小鼠的NETs水平从而有效改善血脂异常的作用机制可能与调控Tbx21、RORγt、Gata3因子，影响Th1/Th2、Th17/Treg分化有关。

关键词

山楂提取物 / 血脂异常 / 炎症免疫调节 / NETs / T细胞分化

Abstract

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Objective

To investigate the mechanism of Shanzha（Hawthorn）extract affecting T cell differentiation and regulating blood lipid level in dyslipidemic mice through neutrophil extracellular trap（NETs）.

Methods

Fifty male 6-week-old C57BL/6 J mice were acclimatized for 1 week, 10 mice were fed with normal chow and 40 mice were fed with 60% high-fat chow to establish a high-fat mouse model. 4 weeks after modeling, the high-fat mice were randomly divided into a high-fat diet（HFD）group, a HFD + Shanzha（Hawthorn）extract group, and a HFD + NETs inhibitor carrier solvent group, HFD + NETs inhibitor GSK484 group. The mice in the HFD + Hawthorn extract group were treated with Shanzha（Hawthorn）extract by gavage［5.2 g/（kg·d）］. The mice in the HFD + NETs inhibitor GSK484 group were intraperitoneally injected with GSK484［4 mg/（kg·d）］. The mice in the HFD + NETs inhibitor carrier solvent group were intraperitoneally injected with an equal amount of carrier solvent, and the mice in the control group and the HFD group were injected with an equal amount of distilled water at the same time. The equal amount of the distilled water was administered orally. After 4 weeks of drug administration, the levels of serum total cholesterol, triglyceride, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were measured by biochemical analyzer. The levels of serum interferon-γ（IFN-γ）, interleukin-4（IL-4）, interleukin-10（IL-10）, interleukin-17A（IL-17A）and interleukin-21（IL-21）were measured by enzyme-linked immunosorbent assay（ELISA）. The immunofluorescence double staining was used for the expressions of neutrophil myeloperoxidase（MPO）and citrullinated histone（CitH3）to analyze the formation of NETs, and Western blotting was used for the protein expressions of peripheral blood mononuclear cell T-box transcription factor 21（TBx21）, Gata-binding protein 3（Gata-3）, retinoic acid-related orphan nuclear receptor γt（RORγt）, forkhead-like transcription factor 3（Foxp3）and B-cell lymphoma 6（Bcl-6）.

Results

Compared with those in the normal control group, the high-fat diet mice showed significant increase in body weights, significant increase in the levels of TC, TG and LDL-C, significant decrease in HDL-C levels, significant increase in the levels of IFN-γ, IL-17A and IL-21, and significant decrease in the levels of IL-4 and IL-10, significant increase in the expression levels of MPO and CitH3, and significant increase in the expression levels of protein expressions of Tbx21 and RORγt in the peripheral blood, and significant decrease in the levels of Gata3, Foxp3 and Bcl-6. Compared with those in the HDF group, the mice in the HFD + Shanzha（Hawthorn）extract group and the HFD + NETs inhibitor GSK484 group had significantly lower body weights, significantly lower levels of TC, TG and LDL-C, significantly higher levels of HDL-C, significantly lower levels of IFN-γ, whereas IL-10 was significantly increased in the HFD + Shanzha（Hawthorn）extract group compared to that in the HFD group, and there was no significant difference in the HFD + NETs inhibitor GSK484 group. Compared to those in the HFD group, in the HFD + Shanzha（Hawthorn）extract and HFD + NETs inhibitor GSK484 groups, the expression levels of MPO and CitH3 dropped significantly. The protein expressions of Tbx21 and RORγt decreased notably, while the Gata3 protein expression increased. Bcl-6 and Foxp3 in the HFD + Shanzha（Hawthorn）extract group increased significantly, but in the HFD + NETs inhibitor GSK484 group, Foxp3 showed no significant change.

Conclusions

The mechanism of action of Shanzha（Hawthorn）extract may be related to the regulation of factors such as Tbx21, RORγt and Gata3, which affect Th1/Th2 and Th17/Treg differentiation, by decreasing the level of NETs in dyslipidemic mice and thus effectively ameliorating dyslipidemia.

Key words

Shanzha（Hawthorn）extract / dyslipidemia / inflammatory immunomodulation / NETs / T cell differentiation

引用本文

周碧聪, 杨莺. 山楂提取物通过NETs影响T细胞调控血脂异常的作用机制研究. 中华中医药学刊, 2026 , 44 (3) : 55 -59 . DOI: 10.13193/j.issn.1673-7717.2026.03.010

Bicong ZHOU, Ying YANG. Mechanism of Shanzha（Hawthorn）Extract in Regulating Dyslipidemia by Affecting T Cells Through NETs[J]. Chinese Archives of Traditional Chinese Medicine, 2026 , 44 (3) : 55 -59 . DOI: 10.13193/j.issn.1673-7717.2026.03.010

基金

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国家自然科学基金项目(81603605)
辽宁省科学技术应用基础研究计划项目(2023JH2/101300057)

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2026年第44卷第3期

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doi: 10.13193/j.issn.1673-7717.2026.03.010

首发时间：2026-10-14
出版时间：2026-03-10

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基金

国家自然科学基金项目(81603605)

辽宁省科学技术应用基础研究计划项目(2023JH2/101300057)

作者信息

^1.辽宁中医药大学，辽宁沈阳 110847

^2.辽宁中医药大学附属医院，辽宁沈阳 110032

通讯作者:

杨莺（1976 -），女，辽宁沈阳人，主任医师，博士研究生导师，博士，研究方向：中西医结合防治心血管疾病。E-mail：yy20170225@sina.com。

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https://castjournals.cast.org.cn/joweb/zhzyyxk/CN/10.13193/j.issn.1673-7717.2026.03.010

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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