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目的 观察姜黄素对转化生长因子-β1(Transforming growth factor-β1,TGF-β1)诱导的心脏成纤维细胞表达神经生长因子(Nerve growth factor, NGF)和炎症因子的影响，并探讨其可能的作用机制。方法 在体外通过TGF-β1刺激心脏成纤维细胞，模拟心肌梗死(Myocardial infarction, MI)模型。分组为Control组、TGF-β1组、美托洛尔(Myto)组，姜黄素微、低、中、高剂量(CCM-5、10、20、40)组。造模时间为48 h,药物处理时间为48 h。使用RT-qPCR检测NGF、Hes1、Hey1、NICD的mRNA表达水平，Western blot法检测NGF、Hes1、Hey1、NICD的蛋白表达水平，Elisa检测细胞上清中炎症因子IL-1β、TNF-α含量。结果 与Control组比较，TGF-β1组细胞中NGF、Hes1、Hey1、NICD的mRNA及其蛋白表达水平明显升高(P<0.05),细胞上清中IL-1β、TNF-α含量明显升高(P<0.05)。与TGF-β1组比较，CCM-5组、CCM-10组、CCM-20组、CCM-40组的NGF、Hes1、Hey1、NICD的mRNA及蛋白表达水平与IL-1β、TNF-α含量均有不同程度的降低，部分组间比较差异有统计学意义(P<0.05),并且这些指标具有姜黄素浓度依赖性。结论 姜黄素可以下调TGF-β1诱导的心脏成纤维细胞中NGF和IL-1β、TNF-α的表达，具有抗交感神经重构和抗炎作用，其机制可能与Notch信号通路的活化有关。
Abstract：Objective To observe the effect of curcumin on the expression of nerve growth factor(NGF) and inflammatory factors in cardiac fibroblasts induced by transforming growth factor-β1(TGF-β1), and to explore the possible mechanism of action. Methods Cardiac fibroblasts were stimulated by TGF-β1 in vitro to simulate myocardial infarction(MI) model. They were divided into control group, TGF-β1 group, metoprolol(Myto) group and curcumin small, low, medium and high dose(CCM 5, 10, 20, 40) groups. The modeling time was 48 hours, and the drug treatment time was 48 hours. The mRNA expression levels of NGF, Hes1, Hey1 and NICD were detected by RT-qPCR, the protein expression levels of NGF, Hes1, Hey1 and NICD were detected by western blot, and the contents of inflammatory factors IL-1β and TNF-α in the cell supernatant were detected by Elisa. Results Compared with control group, the expression levels of NGF, Hes1, Hey1 and NICD mRNA and their proteins in TGF-β1 group were significantly increased(P<0.05), the contents of IL-1β and TNF-α in cell supernatant were significantly increased(P<0.05). Compared with TGF-β1 group, the expression levels of NGF, Hes1, Hey1 and NICD mRNA and their proteins in CCM-5 group, CCM-10 group, CCM-20 group and CCM-40 group were decreased to varying degrees, as well as the contents of IL-1β and TNF-α. The comparison among the groups were statistically significant(P<0.05). These indicators were concentration dependent on curcumin. Conclusion Curcumin can down-regulate the expression of NGF, IL-1β and TNF-α in cardiac fibroblasts induced by TGF-β1, and it has anti-sympathetic remodeling and anti-inflammatory effects, which may be related to the activation of Notch signaling pathway.
[1] 国家卫生健康委员会.中国卫生健康统计年鉴2020[M].北京：中国协和医科大学出版社，2020.
[2] PERERA D,MORGAN H P,RYAN M,et al.Arrhythmia and death following percutaneous revascularization in ischemic left ventricular dysfunction:prespecified analyses from the REVIVED-BCIS2 trial[J].Circulation,2023,148(11):862-871.
[3] ZEPPENFELD K,TFELT-HANSEN J,DE RIVA M,et al.2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death[J].Eur Heart J,2022,43(40):3997-4126.
[4] DUSI V,DE FERRARI G M,SCHWARTZ P J.There are 100 ways by which the sympathetic nervous system can trigger life-threatening arrhythmias[J].Eur Heart J,2020,41(23):2180-2182.
[5] GIANNINO G,BRAIA V,GRIFFITH BROOKLES C,et al.The intrinsic cardiac nervous system:from pathophysiology to therapeutic implications[J].Biology(Basel),2024,13(2):105.
[6] LIU X,CHEN B,CHEN J,et al.A cardiac-targeted nanozyme interrupts the inflammation-free radical cycle in myocardial infarction[J].Adv Mater,2024,36(2):e2308477.
[7] AN P,WAN S,LUO Y,et al.Micronutrient supplementation to reduce cardiovascular risk[J].J Am Coll Cardiol,2022,80(24):2269-2285.
[8] KUNNUMAKKARA A B,BORDOLOI D,PADMAVATHI G,et al.Curcumin,the golden nutraceutical:multitargeting for multiple chronic diseases[J].Br J Pharmacol,2017,174(11):1325-1348.
[9] LUISIER R,ANDREASSI C,FOURNIER L,et al.The predicted RNA-binding protein regulome of axonal mRNAs[J].Genome Res,2023,33(9):1497-1512.
[10] TAN A Y,ELHARRIF K,CARDONA-GUARACHE R,et al.Persistent proarrhythmic neuralremodeling despite recoveryfrompremature ventricular contraction-induced cardiomyopathy[J].J Am Coll Cardiol,2020,75(1):1-13.
[11] BLAKE M R,PARRISH D C,STAFFENSON M A,et al.Chondroitin sulfate proteoglycan 4,6 sulfation regulates sympathetic nerve regeneration after myocardial infarction[J].Elife,2022,11:e78387.
[12] FUKUYAMA Y,KUBO M,HARADA K.Neurotrophic natural products[J].Prog Chem Org Nat Prod,2024,123:1-473.
[13] NODERA M,OIKAWA M,NAKAZATO K,et al.Sympathetic nervous remodeling is induced in the intermediolateral nucleus after myocardial infarction-Role of BDNF-TrkB axis[J].Neurosci Lett,2018,685:114-123.
[14] ALEX L,TULETA I,HERNANDEZ S C,et al.Cardiac pericytes acquire a fibrogenic phenotype and contribute to vascular maturation after myocardial infarction[J].Circulation,2023,148(11):882-898.
[15] 李家立.连夏宁心颗粒对心肌梗死后大鼠心脏自主神经重构的影响[D].北京：北京中医药大学，2015.
[16] 李家立，李平，马洪皓，等.连夏配方颗粒对心梗后大鼠心肌组织酪氨酸羟化酶mRNA、乙酰胆碱酯酶mRNA表达的影响[J].环球中医药，2015,8(2):162-165.
[17] CAI S,ZHAO M,ZHOU B,et al.Mitochondrial dysfunction in macrophages promotes inflammation and suppresses repair after myocardial infarction[J].J Clin Invest,2023,133(4):e159498.
[18] WEI K,NGUYEN H N,BRENNER M B.Fibroblast pathology in inflammatory diseases[J].J Clin Invest,2021,131(20):e149538.
[19] MASSAGUé J,SHEPPARD D.TGF-β signaling in health and disease[J].Cell,2023,186(19):4007-4037.
[20] OUYANG S,YAO Y H,ZHANG Z M,et al.Curcumin inhibits hypoxia inducible factor-1α-induced inflammation and apoptosis in macrophages through an ERK dependent pathway[J].Eur Rev Med Pharmacol Sci,2019,23(4):1816-1825.
[21] 范爱月，吴相君，邵爱民，等.姜黄素对动脉粥样硬化家兔血脂、炎性因子及内皮功能的影响[J].中国中医药科技，2020,27(3):373-375.
[22] 贺兆发，刘聪辉，刘春辉，等.姜黄素对心肌梗死大鼠心肌交感神经萌出及caspase-3表达的影响[J].中国分子心脏病学杂志，2015,15(3):1318-1321.
[23] GHAFOURI-FARD S,GLASSY M C,ABAK A,et al.The interaction between miRNAs/lncRNAs and Notch pathway in human disorders[J].Biomed Pharmacother,2021,138:111496.
[24] SPRINZAK D,BLACKLOW S C.Biophysics of Notch signaling[J].Annu Rev Biophys,2021,50:157-189.
[25] ZHENG D,TAO M,LIANG X,et al.p66Shc regulates podocyte autophagy in high glucose environment through the Notch-PTEN-PI3K/Akt/mTOR pathway[J].Histol Histopathol,2020,35(4):405-415.
[26] SUN Y,PINTO C,CAMUS S,et al.Splenic marginal zone B lymphocytes regulate cardiac remodeling after acute myocardial infarction in mice[J].J Am Coll Cardiol,2022,79(7):632-647.
[27] MARTíN-BóRNEZ M,FALCóN D,MORRUGARES R,et al.New insights into the reparative angiogenesis after myocardial infarction[J].Int J Mol Sci,2023,24(15):12298.
[28] 历志.Notch信号调控巨噬细胞参与心梗重塑的作用和分子机制研究[D].西安：第四军医大学，2012.
基本信息:
中图分类号:R285.5
引用信息:
[1]刘玉旋,王新慧,杨阳,等.姜黄素对TGF-β1诱导的心脏成纤维细胞表达NGF、IL-1β、TNF-α的影响及机制研究[J].新疆医科大学学报,2024,47(06):772-777+784.
基金信息:
国家自然科学基金项目(81960852); 中国中医科学院优秀青年科技人才培养专项项目(ZZ16-YQ-001)
2024-06-15
2024-06-15