[1]国涛 蔺雪峰 李阳 罗星.犬尿酸抑制M1型巨噬细胞极化改善盐敏感性高血压的作用与机制研究[J].心血管病学进展,2026,(2):186.[doi:10.16806/j.cnki.issn.1004-3934.2026.02.017]
　GUO Tao,LIN Xuefeng,LI Yang,et al.The effect and Mechanism of Kynurenic Acid on Salt-Sensitive Hypertension by Inhibiting the M1 Polarization of Macrophages[J].Advances in Cardiovascular Diseases,2026,(2):186.[doi:10.16806/j.cnki.issn.1004-3934.2026.02.017]
点击复制

犬尿酸抑制M1型巨噬细胞极化改善盐敏感性高血压的作用与机制研究()

《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2026年2期
页码:
186
栏目:
论著
出版日期:
2026-02-25

文章信息/Info

Title:
The effect and Mechanism of Kynurenic Acid on Salt-Sensitive Hypertension by Inhibiting the M1 Polarization of Macrophages
作者:
国涛1 蔺雪峰 2 李阳 2 罗星 3
(1.内蒙古科技大学包头医学院研究生院,内蒙古 包头 014040;2.内蒙古科技大学包头医学院第一附属医院心内一科,内蒙古 包头 014010;3.哈尔滨医科大学附属第二医院心内科,黑龙江 哈尔滨 150001)
Author(s):
GUO Tao1; LIN Xuefeng2; LI Yang2; LUO Xing3
(1.Graduate School of Baotou Medical College,Inner Mongolia University of Science and Technology,Baotou 014040,Neimenggu,China;2.Department of Cardiology I,First Affiliated Hospital of Baotou Medical College,Inner Mongolia University of Science and Technology,Baotou 014010,Neimenggu,China;3.Department of Cardiology,The Second Affiliated Hospital of Harbin Medical University,Harbin 150001,Heilongjiang,China)
关键词:
盐敏感性高血压; 犬尿酸; 巨噬细胞极化
Keywords:
Salt-sensitive hypertension; Kynurenic acid; Polarization of macrophage
DOI:
10.16806/j.cnki.issn.1004-3934.2026.02.017
摘要:
目的 证实犬尿酸可改善盐敏感性高血压病变的作用，同时阐明犬尿酸通过抑制 NF-κB信号转导途径激活进而抑制巨噬细胞向M1极化，改善盐敏感性高血压病变的具体机制。方法 动物实验以高盐饮食构建盐敏感性高血压大鼠模型，并予犬尿酸干预，8周后检测肾纤维化、血压、血肌酐、尿素氮、巨噬细胞M1极化及外周血单核细胞NF-κB通路关键蛋白。细胞实验以 血管紧张素Ⅱ处理骨髓巨噬细胞，设抑制剂阳性对照组及犬尿酸干预组，检测M1极化及NF-κB通路关键蛋白表达情况。结果 动物实验显示，犬尿酸可显著降低高盐饮食盐敏感性高血压大鼠的收缩压、血肌酐和尿素氮，减轻肾纤维化，抑制肾间质巨噬细胞M1极化及外周血单核细胞NF-κB通路活化；细胞实验证实，犬尿酸能抑制巨噬细胞M1极化并抑制NF-κB通路激活。 结论 犬尿酸通过抑制巨噬细胞NF-κB通路活化，减少其向M1极化，从而改善盐敏感性高血压病变。
Abstract:
Objective??/b>To confirm the effect of kynurenic acid (KA) on protecting salt-sensitive hypertension,and to clarify the specific mechanism of kynurenate in inhibiting macrophage polarization through NF-κB signaling pathway to improve renal injury in salt-sensitive hypertension. Methods??/b>Rat models of salt-sensitive hypertension were established by high-salt diet and treated with kynura. After 8 weeks,renal fibrosis,blood pressure,serum creatinine,urea nitrogen,macrophage M1 polarization and key proteins of NF-κB pathway in peripheral blood monocytes were detected. In the cell experiment,the bone marrow macrophages were treated with AngⅡ,and the inhibitor positive control and KA intervention group were set up. The M1 polarization and the expression of key proteins in the NF-κB pathway were detected. Results??/b>Animal experiments have shown that KA can significantly reduce systolic blood pressure,serum creatinine and urea nitrogen in salt-sensitive rats with high-salt diet,alleviate renal fibrosis,inhibit M1 polarization of renal macrophages and activation of NF-κB pathway in peripheral blood monocytes. In vitro experiments confirmed that KA inhibited the M1 polarization of macrophages and reduced the activation of NF-κB pathway. Conclusion?#160 KA improves salt-sensitive hypertension by inhibiting the activation of NF-κB pathway in macrophages and reducing their polarization to M1.

参考文献/References:

[1]Masenga SK,Pilic L,Kirabo A. Salt taste and salt sensitive hypertension in HIV[J]. Curr Hypertens Rep,2023,25(3):25-33.

[2]Shremo Msdi A,Haghparast A,Garey KW,et al. Microbiome-based therapeutics for salt-sensitive hypertension:a scoping review[J]. Nutrients,2025,17(5):825.

[3]Cervenka I,Agudelo LZ,Ruas JL. Kynurenines:tryptophan’s metabolites in exercise,inflammation,and mental health[J]. Science,2017,357(6349):eaaf9794.

[4]Meier TB,Savitz J. The kynurenine pathway in traumatic brain injury:implications for psychiatric outcomes[J]. Biol Psychiatry,2022,91(5):449-458.

[5]Ballesteros J,Rivas D,Duque G. The role of the kynurenine pathway in the pathophysiology of frailty,sarcopenia,and osteoporosis[J]. Nutrients,2023,15(14):3132.

[6]Sheibani M,Shayan M,Khalilzadeh M,et al. Kynurenine pathway and its role in neurologic,psychiatric,and inflammatory bowel diseases[J]. Mol Biol Rep,2023,50(12):10409-10425.

[7]Lu J,Bai Z,Kuang X,et al.[High-salt exposure induces macrophage polarization to promote proliferation and phenotypic transformation of co-cultured renal fibroblasts][J]. Nan Fang Yi Ke Da Xue Xue Bao,2020,40(10):1472-1479.

[8]Feng X,Zhu S,Qiao J,et al. CX3CL1 promotes M1 macrophage polarization and osteoclast differentiation through NF-κB signaling pathway in ankylosing spondylitis in vitro[J]. J Transl Med,2023,21(1):573.

[9]Bailey MA. Salbutamol and salt-sensitive hypertension[J]. Kidney Int,2021,100(2):272-275.

[10]Mary S,Boder P,Padmanabhan S,et al. Role of uromodulin in salt-sensitive hypertension[J]. Hypertension,2022,79(11):2419-2429.

[11]Locati M,Curtale G,Mantovani A. Diversity,mechanisms,and significance of macrophage plasticity[J]. Annu Rev Pathol,2020,15:123-147.

[12]Pitzer A,Elijovich F,Laffer CL,et al. DC ENaC-dependent inflammasome activation contributes to salt-sensitive hypertension[J]. Circ Res,2022,131(4):328-344.

[13]Ertuglu LA,Mutchler AP,Yu J,et al. Inflammation and oxidative stress in salt sensitive hypertension;the role of the NLRP3 inflammasome[J]. Front Physiol,2022,13:1096296.

[14]Veiras LC,Bernstein EA,Cao D,et al. Tubular IL-1β induces salt sensitivity in diabetes by activating renal macrophages[J]. Circ Res,2022,131(1):59-73.

[15]Yang XF,Wang H,Huang Y,et al. Myeloid angiotensin Ⅱ type 1 receptor mediates macrophage polarization and promotes vascular injury in DOCA/salt hypertensive mice[J]. Front Pharmacol,2022,13:879693.

[16]Navaneethabalakrishnan S,Goodlett BL,Smith HL,et al. Differential changes in end organ immune cells and inflammation in salt-sensitive hypertension:effects of increasing M2 macrophages[J]. Clin Sci (Lond),2024,138(14):921-940.

[17]Walczak K,Wnorowski A,Turski WA,et al. Kynurenic acid and cancer:facts and controversies[J]. Cell Mol Life Sci,2020,77(8):1531-1550.

[18]Gaffen SL,Jain R,Garg AV,et al. The IL-23-IL-17 immune axis:from mechanisms to therapeutic testing[J]. Nat Rev Immunol,2014,14(9):585-600.

[19]Tiszlavicz Z,Németh B,Fül?p F,et al. Different inhibitory effects of kynurenic acid and a novel kynurenic acid analogue on tumour necrosis factor-α (TNF-α) production by mononuclear cells,HMGB1 production by monocytes and HNP1-3 secretion by neutrophils[J]. Naunyn Schmiedebergs Arch Pharmacol,2011,383(5):447-455.

[20]Mándi Y,Endrész V,Mosolygó T,et al. The Opposite effects of kynurenic acid and different kynurenic acid analogs on tumor necrosis factor-α (TNF-α) production and tumor necrosis factor-stimulated gene-6 (TSG-6) expression[J]. Front Immunol,2019,10:1406.

[21]Wyant GA,Yu W,Doulamis IP,et al. Mitochondrial remodeling and ischemic protection by G protein-coupled receptor 35 agonists[J]. Science,2022,377(6606):621-629.

相似文献/References:

[1]宋志平 杨永健.GPR 35在心血管疾病中的研究进展[J].心血管病学进展,2019,(9):1304.[doi:10.16806/j.cnki.issn.1004-3934.2019.09.031]
　SONG Zhiping,YANG Yongjian.The Current Progress of GPR 35 in Cardiovascular Disease[J].Advances in Cardiovascular Diseases,2019,(2):1304.[doi:10.16806/j.cnki.issn.1004-3934.2019.09.031]
[2]马婕 王文娟 余静.抗血管生成靶向药物致高血压的机制进展[J].心血管病学进展,2023,(9):841.[doi:10.16806/j.cnki.issn.1004-3934.2023.09.017]
　MA Jie,WANG Wenjuan,YU Jing.Mechanism of Hypertension Induced by Antiangiogenic Targeted Drugs[J].Advances in Cardiovascular Diseases,2023,(2):841.[doi:10.16806/j.cnki.issn.1004-3934.2023.09.017]
[3]牛文慧 王蕾.犬尿酸-G蛋白偶联受体35信号通路在代谢性心血管疾病中的研究进展[J].心血管病学进展,2026,(1):1.[doi:10.16806/j.cnki.issn.1004-3934.2026.01.001]
　NIU Wenhui,WANG Lei.Kynurenic Acid-G Protein-Coupled Receptor 35 Signaling Pathway in Metabolic Cardiovascular Diseases[J].Advances in Cardiovascular Diseases,2026,(2):1.[doi:10.16806/j.cnki.issn.1004-3934.2026.01.001]

更新日期/Last Update: 2026-05-28