[1]林 琳,樊 刚,李 青,等.白藜芦醇对实验性自身免疫性心肌炎大鼠心肌巨噬细胞极化及心肌炎性损伤的影响[J].陕西医学杂志,2025,54(1):27-32.[doi:DOI:10.3969/j.issn.1000-7377.2025.01.005]
　LIN Lin,FAN Gang,LI Qing,et al.The influence of resveratrol on macrophage polarization and myocardial inflammatory injury in rats with experimental autoimmune myocarditis[J].,2025,54(1):27-32.[doi:DOI:10.3969/j.issn.1000-7377.2025.01.005]
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白藜芦醇对实验性自身免疫性心肌炎大鼠心肌巨噬细胞极化及心肌炎性损伤的影响
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年1期
页码:
27-32
栏目:
基础研究
出版日期:
2025-01-05

文章信息/Info

Title:
The influence of resveratrol on macrophage polarization and myocardial inflammatory injury in rats with experimental autoimmune myocarditis
作者:
林 琳1; 樊 刚2; 李 青1; 朱文静1; 薛嘉虹1; 魏 瑾1
( 1.西安交通大学第二附属医院心血管病院,陕西 西安 710004; 2.陕西中医药大学附属咸阳市中心医院,陕西 咸阳712000)
Author(s):
LIN Lin; FAN Gang; LI Qing; ZHU Wenjing; XUE Jiahong; WEI Jin
(Department of Cardiology,the Second Affiliated Hospital of Xi'an Jiaotong University,Xi' an 710004,China)
关键词:
巨噬细胞极化;  炎症因子;  白藜芦醇;  实验性自身免疫性心肌炎;  心肌损伤;  人NOD样受体家组蛋白3炎症小体
Keywords:
Macrophage polarization;  Inflammatory factors;  Resveratrol;  Experimental autoimmune myocarditis;  Myocardial injury;  NLRP3 inflammasome
分类号:
R 542.2
DOI:
DOI:10.3969/j.issn.1000-7377.2025.01.005
文献标志码:
A
摘要:
目的:探讨白藜芦醇(Res)对实验性自身免疫性心肌炎(EAM)大鼠心肌巨噬细胞极化及炎性损伤的影响。方法:建立EAM大鼠模型,分为对照组、EAM组、Resveratrol组,通过免疫荧光、HE染色观察心肌组织巨噬细胞浸润程度并对心肌病理损伤进行评分; 采用Realtime PCR检测巨噬细胞极化标记分子诱生型一氧化氮合酶(iNOS)、精氨酸酶1(Arg1)及炎症因子白细胞介素6(IL-6)、白细胞介素1β(IL-1β)、肿瘤坏死因子-α(TNF-α)的表达变化,Western blot检测NLRP3炎性小体蛋白组分的表达变化。结果:EAM组大鼠心肌组织可见大量巨噬细胞浸润,伴有明显的心肌纤维断裂、溶解; IL-6、IL-1β、TNF-α、iNOS mRNA表达均较Control组显著增加(分别为P<0.05,P<0.05,P<0.01,P<0.01),而Arg1表达较Control组显著减少(P<0.05); Resveratrol可减少EAM大鼠心肌组织巨噬细胞浸润数量及心肌病理损伤积分(均P<0.05),减少IL-6、IL-1β、TNF-α、iNOS mRNA的表达(均P<0.05),增加Arg1的表达(P<0.01)。同时,与Control组比较,EAM大鼠心肌组织NLRP3和Caspase-p10、pro-Caspase-1及IL-1β蛋白表达明显升高(均P<0.05),Resveratrol可显著减少人NOD样受体家组蛋白3(NLRP3)、Caspase-p10、pro-Caspase-1及IL-1β蛋白表达,差异具有统计学意义(均P<0.05)。结论:巨噬细胞浸润并向M1型极化参与EAM大鼠心肌炎性损伤; Res可能通过抑制M1型巨噬细胞向M2型极化、NLRP3炎症小体激活及相关炎性因子释放减轻EAM心肌损伤。
Abstract:
Objective:To explore the effects of resveratrol on myocardial macrophage polarization and inflammatory injury in experimental autoimmune myocarditis(EAM)rats.Methods:Experimental myocarditis model was established and randomly divided into 3 groups:Control group(Control),EAM model group(EAM)and Resveratrol treatment group(Resveatrol).The degree of macrophage infiltration were detected by immunofluorescence and the degree of myocardial injury was detected by HE stain.The expression of markers(iNOS and Arg1)of M1 and M2 macrophage and inflammatory factors were detected by Realtime PCR.Western blot was used to detect the expression changes of NLRP3 inflammasome protein components.Results:Large numbers of macrophages were observed infiltrating the myocardial tissue of EAM group rats,accompanied by significant myocardial fiber rupture and dissolution; The mRNA expression of IL-6,IL-1β,TNF-α,and iNOS were significantly increased in the control group compared to the control group(P<0.05,P<0.05,P<0.01,P<0.01),The expression of Arg1 was significantly reduced compared to the control group(P<0.05),and the difference was statistically significant; Resveratrol can reduce the infiltration of macrophages and myocardial pathological injury score in EAM rats' myocardial tissue(P<0.05),decrease the expression of IL-6,IL-1β,TNF-α,iNOS mRNA(P<0.05),and increase the expression of Arg1(P<0.01),with statistical significance.Meanwhile,compared with the Control group,the protein expression of NLRP3 and Caspase-p10,pro-Caspase-1,and IL-1 β in the myocardial tissue of EAM rats was significantly increased.Resveratrol significantly reduced the protein expression of NLRP3,Caspase-p10,pro-Caspase-1,and IL-1 β(all P<0.05),and the difference was statistically significant.Conclusion:Macrophage infiltration and polarization towards M1 type are associated with myocardial injury in EAM rats; Res may alleviate EAM myocardial injury by inhibiting polarization of M1 macrophages towards M2,activation of NLRP3 inflammasomes,and reduced release of inflammatory factors.

参考文献/References:

[1] YULONG X,ZHENHAO Z,SHANGYU L,et al.Lupeol alleviates autoimmune myocarditis by suppressing macrophage pyroptosis and polarization via PPARα/LACC1/NF-κB signaling pathway [J].Phytomedicine,2024,123:155193.
[2] XU S,XU C,XU J,et al.Macrophage heterogeneity and its impact on myocardial ischemia-reperfusion injury:An integrative review [J].Journal of Inflammation Research,2023,16:5971-5987.
[3] ROJAS M G,ZIGMOND Z M,PEREIRA-SIMON S,et al.The intricate cellular ecosystem of human peripheral veins as revealed by single-cell transcriptomic analysis[J].PLoS One,2024,19(1):e0296264.
[4] TAO L,LINLIN C,YIYAN Y,et al.Resveratrol alleviates hypoxia/reoxygenation injury-induced mitochondrial oxidative stress in cardiomyocytes[J].Molecular Medicine Reports,2019,19(4):2774-2780.
[5] 林琳,闫蕊,刘昕,等.巨噬细胞移动抑制因子在实验性自身免疫性心肌炎大鼠心肌中的表达及白藜芦醇的治疗作用[J].西安交通大学学报(医学版),2018,39(2):232-236.
[6] LUO J,CHEN M,JI H,et al.Regulates macrophage polarization via the lipophage-NLRP3 inflammasome to ameliorate atherosclerosis in ApoE-/- mice[J].Journal of Functional Foods,2024,118:106280.
[7] AJCZAK M P,JZWIK K.Artificial intelligence and myocarditis:A systematic review of current applications[J].Heart Fail Rev,2024,29(6):1217-1234.
[8] 刘锋锋,郑建杰,刘淼淼.体外膜肺氧合治疗对成人暴发性心肌炎患者细胞因子表达谱的影响[J].陕西医学杂志,2022,51(4):429-432,436.
[9] BERGER S,CECCARINI G,SCABIA G,et al.Lipodystrophy and obesity are associated with decreased number of T cells with regulatory function and pro-inflammatory macrophage phenotype[J].International Journal of Obesity,2017,41(11):1676.
[10] PUMMERER C,BERGER P,FR HWIRTH M,et al.Cellular infiltrate,major histocompatibility antigen expression and immunopathogenic mechanisms in cardiac myosin-induced myocarditis [J].Laboratory Investigation,1991,65(5):538-547.
[11] KANG L,WEI X,QIANG G,et al.Differential macrophage polarization in male and female BALB/c mice infected with Coxsackievirus B3 defines susceptibility to viral myocarditis [J].Circulation Research,2009,105(4):353-364.
[12] GÖSER S,OTTL R,BRODNER A,et al.Critical role for monocyte chemoattractant protein-1 and macrophage inflammatory protein-1α in induction of experimental autoimmune myocarditis and effective anti-monocyte chemoattractant protein-1 gene therapy [J].Circulation,2005,112(22):3400-3407.
[13] GAO S,ZHOU J,LIU N,et al.Curcumin induces M2 macrophage polarization by secretion IL-4 and/or IL-13[J].Journal of Molecular & Cellular Cardiology,2015,85(3):131.
[14] 周子程,张润峰.巨噬细胞在心肌梗死中的作用研究进展[J].陕西医学杂志,2024,53(5):714-717.
[15] 刘华亭,郑博文,陈晨,等.基于NLRP3/Caspase-1/IL-1β信号通路探讨复方蛇龙胶囊对膜性肾病大鼠的作用[J].陕西中医,2023,44(6):709-716.
[16] JIHUA T,SIJIA C,JING W,et al.S1P/S1PR1 axis promotes macrophage M1 polarization through NLRP3 inflammasome activation in Lupus nephritis[J].Molecular Immunology,2023,160:55-66.
[17] 郑美佳,贾瑞,闫曙光,等.巨噬细胞中YAP协同NF-κBp65激活NLRP3炎症小体促进M1型极化[J].现代免疫学,2023,43(3):233-238,244.
[18] 华荣,陈瑶.益母草碱抑制NLRP3炎症小体过度激活调控巨噬细胞M1/M2表型分化[J].药学实践杂志,2021,39(2):143-147.
[19] 吴文婷,李敏,蒲文娟.白藜芦醇对慢性阻塞性肺疾病大鼠 p38丝裂原活化蛋白激酶/核因子-κB信号通路的影响[J].陕西医学杂志,2023,52(11):1489-1492,1534.
[20] 张晓光,党萍,霍琳,等.衔接蛋白失能同源物2通过抑制NOD样受体热蛋白结构域相关蛋白3对结核性胸膜炎大鼠炎症和氧化应激的影响[J].陕西医学杂志,2024,53(4):468-474.
[21] 金美玲,赖奕宏,敖英.白藜芦醇对M1/M2巨噬细胞极化的作用及其机制[J].时珍国医国药,2018,29(6):1319-1322.
[22] 萧文泽,赵力,邹和建.白藜芦醇促进巨噬细胞M2极化并缓解小鼠急性痛风性关节炎[J].第二军医大学学报,2019,40(8):860-865.
[23] 甘露,张春戬,李莹,等.益气通络汤对Heymann肾炎大鼠蛋白尿及炎症因子的影响[J].保健医学研究与实践,2023,20(12):16-22.

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备注/Memo

备注/Memo:
基金项目:陕西省重点研发计划项目(2024SF-YBXM-005)
更新日期/Last Update: 2025-01-06