Objective To study the effects and mechanisms of tetramethylpyrazine (TMP) on tumor necrosis factor-α (TNF-α)-induced inflammatory injury in human coronary artery endothelial cells (HCAEC). Methods HCAEC were randomly divided into four groups: the control group (no treatment), the model group (treated with TNF-α, 50 ng/mL for 24 hours), the TMP group (pre-treated with TMP, 80 μg/mL for 12 hours followed by TNF-α treatment for 24 hours), and the SIRT1 inhibitor group (pre-treated with TMP and the specific SIRT1 inhibitor EX527 for 12 hours followed by TNF-α treatment for 24 hours). Cell viability was assessed using the CCK-8 method, lactate dehydrogenase (LDH) activity was measured using an LDH assay kit, reactive oxygen species (ROS) levels were observed using DCFH-DA staining, expression of pyroptosis-related proteins was detected by Western blot, and SIRT1 expression was analyzed using immunofluorescence staining. Results Compared to the control group, the model group showed decreased cell viability, increased LDH activity, ROS level and expression of pyroptosis-related proteins, and decreased SIRT1 expression (P<0.05). Compared to the model group, the TMP group exhibited increased cell viability, decreased LDH activity, ROS level and expression of pyroptosis-related proteins, and increased SIRT1 expression (P<0.05). In comparison to the TMP group, the SIRT1 inhibitor group showed decreased cell viability, increased LDH activity, ROS level and expression of pyroptosis-related proteins, and decreased SIRT1 expression (P<0.05). Conclusions TMP may attenuate TNF-α-induced inflammatory injury in HCAEC, which is associated with the inhibition of pyroptosis and activation of the SIRT1 signaling pathway.
Key words
Inflammatory injury /
Tetramethylpyrazine /
SIRT1 /
Pyroptosis /
Human coronary artery endothelial cell
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
1 中华医学会儿科学分会心血管学组, 中华医学会儿科学分会风湿学组, 中华医学会儿科学分会免疫学组, 等. 川崎病诊断和急性期治疗专家共识[J]. 中华儿科杂志, 2022, 60(1): 6-13. PMID: 34986616. DOI: 10.3760/cma.j.cn112140-20211018-00879.
2 陕西省川崎病诊疗中心/陕西省人民医院儿童病院, 国家儿童医学中心/首都医科大学附属北京儿童医院, 上海交通大学医学院附属儿童医院, 等. 中国儿童川崎病诊疗循证指南（2023年）[J]. 中国当代儿科杂志, 2023, 25(12): 1198-1210. PMID: 38112136. PMCID: PMC10731970. DOI: 10.7499/j.issn.1008-8830.2309038.
3 黄敏. 川崎病的早期筛查与临床诊疗规范管理[J]. 上海医学, 2022, 45(8): 524-527. DOI: 10.19842/j.cnki.issn.0253-9934.2022.08.003.
4 Trimm E, Red-Horse K. Vascular endothelial cell development and diversity[J]. Nat Rev Cardiol, 2023, 20(3): 197-210. PMID: 36198871. PMCID: PMC9533272. DOI: 10.1038/s41569-022-00770-1.
5 Lin J, Wang Q, Zhou S, et al. Tetramethylpyrazine: a review on its mechanisms and functions[J]. Biomed Pharmacother, 2022, 150: 113005. PMID: 35483189. DOI: 10.1016/j.biopha.2022.113005.
6 Yang Y, Liu Y, Wang Y, et al. Regulation of SIRT1 and its roles in inflammation[J]. Front Immunol, 2022, 13: 831168. PMID: 35359990. PMCID: PMC8962665. DOI: 10.3389/fimmu.2022.831168.
7 Liu J, Yan Y, Zheng D, et al. Inhibiting microRNA-200a-3p attenuates pyroptosis via targeting the SIRT1/NF-κB/NLRP3 pathway in H2O2-induced HAEC[J]. Aging (Albany NY), 2023, 15(20): 11184-11200. PMID: 37874693. PMCID: PMC10637806. DOI: 10.18632/aging.205121.
8 郑小兰, 张怡. 川崎病内皮细胞模型及其发病机制研究进展[J]. 医学研究杂志, 2019, 48(6): 11-13. DOI: 10.11969/j.issn.1673-548X.2019.06.003.
9 Wang X, Ding YY, Chen Y, et al. MiR-223-3p alleviates vascular endothelial injury by targeting IL6ST in Kawasaki disease[J]. Front Pediatr, 2019, 7: 288. PMID: 31396494. PMCID: PMC6667785. DOI: 10.3389/fped.2019.00288.
10 Yang Y, Wang N, Wang Z, et al. Protective role of forsythoside B in Kawasaki disease-induced cardiac injury: inhibition of pyroptosis via the SIRT1-NF-κB-p65 signaling pathway[J]. Chem Biol Interact, 2024, 392: 110953. PMID: 38471628. DOI: 10.1016/j.cbi.2024.110953.
11 Ding Y, Peng Y, Wu H, et al. The protective roles of liraglutide on Kawasaki disease via AMPK/mTOR/NF-κB pathway[J]. Int Immunopharmacol, 2023, 117: 110028. PMID: 36934674. DOI: 10.1016/j.intimp.2023.110028.
12 Liu Y, Tan Y, Cao G, et al. Bergenin alleviates myocardial ischemia-reperfusion injury via SIRT1 signaling[J]. Biomed Pharmacother, 2023, 158: 114100. PMID: 36538860. DOI: 10.1016/j.biopha.2022.114100.
13 王程浩, 刘芳. 川崎病所致冠状动脉病变的病理改变及结局[J]. 中华实用儿科临床杂志, 2021, 36(22): 1757-1760. DOI: 10.3760/cma.j.cn101070-20210510-00513.
14 Stock AT, Jama HA, Hansen JA, et al. TNF and IL-1 play essential but temporally distinct roles in driving cardiac inflammation in a murine model of Kawasaki disease[J]. J Immunol, 2019, 202(11): 3151-3160. PMID: 30996002. DOI: 10.4049/jimmunol.1801593.
15 Guo M, Liu Y, Shi D. Cardiovascular actions and therapeutic potential of tetramethylpyrazine (active component isolated from Rhizoma Chuanxiong): roles and mechanisms[J]. Biomed Res Int, 2016, 2016: 2430329. PMID: 27314011. PMCID: PMC4893570. DOI: 10.1155/2016/2430329.
16 Shao H, Zhao L, Chen F, et al. Efficacy of ligustrazine injection as adjunctive therapy for angina pectoris: a systematic review and meta-analysis[J]. Med Sci Monit, 2015, 21: 3704-3715. PMID: 26615387. PMCID: PMC4671452. DOI: 10.12659/msm.895362.
17 Seki M, Minami T. Kawasaki disease: pathology, risks, and management[J]. Vasc Health Risk Manag, 2022, 18: 407-416. PMID: 35711626. PMCID: PMC9196282. DOI: 10.2147/VHRM.S291762.
18 齐双辉, 魏兵. 川崎病抗冠状动脉血栓中西药物的应用进展[J]. 中国中西医结合儿科学, 2021, 13(4): 311-316. DOI: 10.3969/j.issn.16743865.2021.04.008.
19 舒梦琦, 戴瑶瑶, 宋丽娟, 等. 基于SIRT1/VEGFA信号通路探讨川芎嗪调节缺血性脑卒中损伤后血管内皮细胞的新生作用研究[J]. 中国中药杂志, 2024, 49(1): 162-174. PMID: 38403349. DOI: 10.19540/j.cnki.cjcmm.20231116.303.
20 Burger F, Baptista D, Roth A, et al. NLRP3 inflammasome activation controls vascular smooth muscle cells phenotypic switch in atherosclerosis[J]. Int J Mol Sci, 2021, 23(1): 340. PMID: 35008765. PMCID: PMC8745068. DOI: 10.3390/ijms23010340.
21 Miao R, Jiang C, Chang WY, et al. Gasdermin D permeabilization of mitochondrial inner and outer membranes accelerates and enhances pyroptosis[J]. Immunity, 2023, 56(11): 2523-2541.e8. PMID: 37924812. PMCID: PMC10872579. DOI: 10.1016/j.immuni.2023.10.004.
22 Zheng D, Liu J, Piao H, et al. ROS-triggered endothelial cell death mechanisms: focus on pyroptosis, parthanatos, and ferroptosis[J]. Front Immunol, 2022, 13: 1039241. PMID: 36389728. PMCID: PMC9663996. DOI: 10.3389/fimmu.2022.1039241.
23 Porritt RA, Zemmour D, Abe M, et al. NLRP3 inflammasome mediates immune-stromal interactions in vasculitis[J]. Circ Res, 2021, 129(9): e183-e200. PMID: 34517723. PMCID: PMC8555446. DOI: 10.1161/CIRCRESAHA.121.319153.
24 Singh V, Ubaid S. Role of silent information regulator 1 (SIRT1) in regulating oxidative stress and inflammation[J]. Inflammation, 2020, 43(5): 1589-1598. PMID: 32410071. DOI: 10.1007/s10753-020-01242-9.
25 Man AWC, Li H, Xia N. The role of sirtuin1 in regulating endothelial function, arterial remodeling and vascular aging[J]. Front Physiol, 2019, 10: 1173. PMID: 31572218. PMCID: PMC6751260. DOI: 10.3389/fphys.2019.01173.
26 Rodriguez-Miguelez P, Pollock JS. Adverse childhood events and cardiovascular diseases: the potential role of Sirt1[J]. Am J Physiol Heart Circ Physiol, 2021, 321(3): H577-H579. PMID: 34448640. PMCID: PMC8461843. DOI: 10.1152/ajpheart.00452.2021.
27 Xia DY, Yuan JL, Jiang XC, et al. SIRT1 promotes M2 microglia polarization via reducing ROS-mediated NLRP3 inflammasome signaling after subarachnoid hemorrhage[J]. Front Immunol, 2021, 12: 770744. PMID: 34899720. PMCID: PMC8653696. DOI: 10.3389/fimmu.2021.770744.
28 Zheng Y, Xu L, Dong N, et al. NLRP3 inflammasome: the rising star in cardiovascular diseases[J]. Front Cardiovasc Med, 2022, 9: 927061. PMID: 36204568. PMCID: PMC9530053. DOI: 10.3389/fcvm.2022.927061.
PDF(2639 KB)
