[1]董文晟 高义鹏 叶云佳 李康 张鑫.鸢尾素对脂多糖诱导的内皮细胞损伤影响[J].心血管病学进展,2025,(1):71.[doi:10.16806/j.cnki.issn.1004-3934.2025.01.016]
　DONG Wensheng,GAO Yipeng,YE Yunjia,et al.Effects of Irisin on Lipopolysaccharide-Induced Endothelial Injury[J].Advances in Cardiovascular Diseases,2025,(1):71.[doi:10.16806/j.cnki.issn.1004-3934.2025.01.016]
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鸢尾素对脂多糖诱导的内皮细胞损伤影响()
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《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2025年1期
页码:
71
栏目:
论著
出版日期:
2025-01-25

文章信息/Info

Title:
Effects of Irisin on Lipopolysaccharide-Induced Endothelial Injury
作者:
董文晟 高义鹏 叶云佳 李康 张鑫
(武汉大学人民医院老年病科 代谢与相关慢病湖北省重点实验室,湖北 武汉430060)
Author(s):
DONG Wensheng; GAO Yipeng; YE Yunjia; LI Kang; ZHANG Xin
(Department of Geriatrics,Renmin Hospital of Wuhan University,Hubei Key Laboratory of Metabolic and Chronic Diseases,Wuhan 430060,Hubei,China) (2023AFB099)(2042023kf0046)(2023KFZZ028)+ E-maildr.zhangxin@whu.edu.cn
关键词:
鸢尾素; 脂多糖; 内皮细胞; 炎症; 氧化应激
Keywords:
Irisin;  Lipopolysaccharide;  Endothelial cells;  Inflammation;  Oxidative stress
DOI:
10.16806/j.cnki.issn.1004-3934.2025.01.016
摘要:
目的 探讨鸢尾素（irisin）对脂多糖（LPS）诱导的内皮细胞损伤影响。 方法 体外培养人脐静脉内皮细胞（HUVECs）并用LPS（100 ng/mL）处理12 h 建立内皮细胞损伤模型，irisin干预组在刺激前给予irisin（20 nmol/L）预处理24 h 。ELISA试剂盒检测细胞培养基中irisin含量；实时定量PCR检测各组炎症指标白细胞介素（IL）-1β、IL-6、单核细胞趋化蛋白-1（MCP-1）、肿瘤坏死因子-α（TNF-α）和氧化应激指标NADPH氧化酶2（Nox2）、核转录因子红系2相关因子2（Nrf2）、超氧化物歧化酶2（SOD2）的mRNA水平，免疫印迹法检测FNDC5蛋白表达、p65蛋白磷酸化和核转位改变；试剂盒检测乳酸脱氢酶（LDH）漏出量、细胞丙二醛（MDA）含量以及过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）的活性；DCFH-DA荧光探针检测活性氧（ROS）水平；CCK-8法检测HUVECs存活率。结果 （1）LPS处理可抑制内皮细胞irisin合成分泌（ P＜0.05）；（2）LPS组细胞存活率明显降低、LDH漏出量增加（P＜0.05），而irisin处理组则明显改善（P＜0.05）；（3）irisin处理组细胞炎症指标IL-1β、MCP-1和TNF-α水平明显下调，p65蛋白磷酸化和核转位水平也受到显著抑制（P＜0.05），但IL-6水平不受影响（P＞0.05）；（4）irisin处理不改变Nrf2 mRNA水平（P＞0.05），但可降低Nox2表达并增加SOD2转录，irisin处理也明显降低细胞MDA含量并增加细胞抗氧化酶CAT和GSH-Px的活性，ROS生成也显著减少（P＜0.05）。结论 irisin对LPS诱导的内皮细胞炎症和氧化应激损伤具有明显的保护作用。
Abstract:
Objective To investigate the effects of irisin on lipopolysaccharide(LPS)-induced endothelial injury. Methods Human umbilical vein endothelial cells(HUVECs) were cultured in vitro and were exposed to LPS (100 ng/mL) for 12 h to generate endothelial injury model. Cells with irisin protection were pretreated with irisin (20 nmol/L) for 24 h. Irisin level in medium was measured by ELISA kit. The mRNA levels of inflammatory markers,including interleukin(IL)-1β,IL-6,monocyte chemotactic protein 1(MCP-1),tumor necrosis factor-α(TNF-α) and oxidative stress indicators ,including reduced nicotinamide adenine dinucleotide phosphate oxidase 2(Nox2),nuclear factor-erythroid 2-related factor 2(Nrf2),superoxide dismutase 2(SOD2) were detected by real-time quantitative PCR,and Western blotting was used to assess FNDC5 protein expression as well as p65 phosphorylation and nuclear translocation. The amount of lactate dehydrogenase (LDH) leakage, intracellular malondialdehyde (MDA) content, and activities of catalase (CAT) and glutathione peroxidase (GSH-Px) were measured by commercial kits. DCFH-DA fluorescent probe was used to measure the intracellular reactive oxygen species (ROS) content. CCK-8 assay was used to detect the survival rate of HUVECs. Results (1) Irisin expression and secretion were significantly decreased by LPS insult ( P＜0.05). (2) LPS significantly decreased cell viability and increased LDH leakage (P＜0.05),which was alleviated by irisin treatment (P＜0.05). (3) Cells with irisin protection exhibited reduced levels of inflammatory markers,including IL-1β,MCP-1 and TNF-α,and p65 phosphorylation as well as nuclear translocation were also inhibited (P＜0.05). However,IL-6 expression was not affected by irisin (P＞0.05). (4) Irisin treatment had no effect on the mRNA level of Nrf2 ( P＞0.05),but Nox2 expression was downregulated ,and SOD2 transcription was upregulated in cells with irisin incubation. Besides ,irisin treatment reduced intracellular MDA content and restored the activities of CAT together with GSH-Px. ROS generation was also significantly attenuated (P＜0.05). Conclusion Irisin exhibits significant protective effect on LPS-triggered inflammatory and oxidative injuries to endothelial cells.

参考文献/References:

[1] 胡灿,唐其柱,张宁,等. 苦参碱对脂多糖诱导的人脐静脉内皮细胞炎性反应及氧化应激的影响[J]. 中华生物医学工程杂志,2018,24(5):305-310.

[2] Huang X,Dai Z,Cai L,et al. Endothelial p110γPI3K mediates endothelial regeneration and vascular repair after inflammatory vascular injury[J]. Circulation,2016,133(11):1093-1103.

[3] 马可,王中英,孙喜伟,等. 肝素在脂多糖诱导急性损伤大鼠血管内皮细胞损伤中的作用及核因子-κB、白介素-1β、白介素-6、肿瘤坏死因子-α变化[J]. 中华实验外科杂志,2017,34(8):1310-1312.

[4] Zhang X,Hu C,Yuan YP,et al. A brief overview about the physiology of fibronectin type Ⅲ domain-containing 5[J]. Cell Signal,2020,76:109805.

[5] Bostr?m P,Wu J,Jedrychowski MP,et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis[J]. Nature,2012,481(7382):463-468.

[6] Song R,Zhao X,Cao R,et al. Irisin improves insulin resistance by inhibiting autophagy through the PI3K/Akt pathway in H9c2 cells[J]. Gene,2021,769:145209.

[7] Pan JA,Zhang H,Lin H,et al. Irisin ameliorates doxorubicin-induced cardiac perivascular fibrosis through inhibiting endothelial-to-mesenchymal transition by regulating ROS accumulation and autophagy disorder in endothelial cells[J]. Redox Biol,2021,46:102120.

[8] Zhu D,Zhang X,Wang F,et al. Irisin rescues diabetic cardiac microvascular injury via ERK1/2/Nrf2/HO-1 mediated inhibition of oxidative stress[J]. Diabetes Res Clin Pract,2022,183:109170.

[9] Deng X,Huang W,Peng J,et al. Irisin alleviates advanced glycation end products-induced inflammation and endothelial dysfunction via inhibiting ROS-NLRP3 inflammasome signaling[J]. Inflammation,2018,41(1):260-275.

[10] Zhang X,Hu C,Kong CY,et al. FNDC5 alleviates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity via activating AKT[J]. Cell Death Differ,2019,27(2):540-555.

[11] Hu C,Zhang X,Hu M,et al. Fibronectin type Ⅲ domain-containing 5 improves aging-related cardiac dysfunction in mice[J]. Aging Cell,2022,21(3):e13556.

[12] Wei H,Sun M,Wang R,et al. Puerarin mitigated LPS-ATP or HG-primed endothelial cells damage and diabetes-associated cardiovascular disease via ROS-NLRP3 signalling[J]. J Cell Mol Med,2024,28(10):e18239.

[13] Hou H,Qin X,Li G,et al. Nrf2-mediated redox balance alleviates LPS-induced vascular endothelial cell inflammation by inhibiting endothelial cell ferroptosis[J]. Sci Rep,2024,14(1):3335.

[14] Yamamoto M,Kensler TW,Motohashi H. The KEAP1-NRF2 system:a thiol-based sensor-effector apparatus for maintaining redox homeostasis[J]. Physiol Rev,2018,98(3):1169-1203.

[15] Moustafa PE,Abo El Nasr NME,Shabana ME,et al. Fisetin mitigates letrozole-induced polycystic ovarian syndrome in rats:crosstalk of AMPK/PI3K/AKT-mediated-Nrf2 antioxidant defense mechanism and the inflammasome NLRP3/NF-κB P65/IL-1β signaling pathways[J]. Naunyn Schmiedebergs Arch Pharmacol,2024,397(10):8077-8088.

[16] Kobayashi EH,Suzuki T,Funayama R,et al. Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription[J]. Nat Commun,2016,7:11624.

[17] Mazur-Bialy AI,Pochec E. The time-course of antioxidant irisin activity:role of the Nrf2/HO-1/HMGB1 axis[J]. Antioxidants (Basel),2021,10(1):88.

[18] Luna-Ceron E,Gonzalez-Gil AM,Elizondo-Montemayor L. Current insights on the role of irisin in endothelial dysfunction[J]. Curr Vasc Pharmacol,2022,20(3):205-220.

[19] Grzeszczuk M,Dziegiel P,Nowinska K. The role of FNDC5/Irisin in cardiovascular disease[J]. Cells,2024,13(3):277.

[20] Zhang X,Hu C,Wu HM,et al. Fibronectin type Ⅲ domain-containing 5 in cardiovascular and metabolic diseases:a promising biomarker and therapeutic target[J]. Acta Pharmacol Sin,2021,42(9):1390-1400.

[21] Ho MY,Wang CY. Role of irisin in myocardial infarction,heart failure,and cardiac hypertrophy[J]. Cells,2021,10(8):2103.

[22] Madhu LN,Somayaji Y,Shetty AK. Promise of irisin to attenuate cognitive dysfunction in aging and Alzheimer’s disease[J]. Ageing Res Rev,2022,78:101637.

[23] Liu JF,Su G,Chen LX,et al. Irisin attenuates apoptosis following ischemia-reperfusion injury through improved mitochondria dynamics and ROS suppression mediated through the PI3K/Akt/mTOR axis[J]. Mol Neurobiol,2023,60(8):4261-4272.

[24] Wang PW,Pang Q,Zhou T,et al. Irisin alleviates vascular calcification by inhibiting VSMC osteoblastic transformation and mitochondria dysfunction via AMPK/Drp1 signaling pathway in chronic kidney disease[J]. Atherosclerosis,2022,346:36-45.

[25] Chen S,Wang L,Gao X,et al. Characterization of serum irisin in patients with severe acute pancreatitis[J]. Eur J Gastroenterol Hepatol,2019,31(8):985-991.

[26] Fan X,Du J,Wang MH,et al. Irisin contributes to the hepatoprotection of dexmedetomidine during intestinal ischemia/reperfusion[J]. Oxid Med Cell Longev,2019,2019:7857082.

[27] Han Z,Ma J,Han Y,et al. Irisin attenuates acute lung injury by suppressing the pyroptosis of alveolar macrophages[J]. Int J Mol Med,2023,51(4):32.

[28] Ma LY,Liu JM,Du GL,et al. Irisin attenuates lipopolysaccharide-induced acute lung injury by downregulating inflammatory cytokine expression through miR-199a-mediated Rad23b overexpression[J]. Exp Cell Res,2021,404(2):112593.

[29] Trettel C,Pelozin B,Barros MP,et al. Irisin:an anti-inflammatory exerkine in aging and redox-mediated comorbidities[J]. Front Endocrinol (Lausanne),2023,14:1106529.

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更新日期/Last Update: 2025-02-26