CHI3L1在川崎病样血管炎小鼠模型冠状动脉损伤中的作用及机制研究

doi:10.7499/j.issn.1008-8830.2309080

摘要
图/表
参考文献(23)
相关文章 (15)
点击分布统计
下载分布统计

全文: PDF (1369 KB) [HTML]
输出: BibTeX | EndNote (RIS) 背景资料

摘要目的探究壳多糖酶3样蛋白1（chitinase-3-like protein 1, CHI3L1）在川崎病（Kawasaki disease, KD）样血管炎小鼠模型冠状动脉损伤中的作用及其潜在机制。方法将4周龄雄性SPF级C57BL/6小鼠随机分为正常对照组和模型组，每组10只。模型组小鼠通过腹腔注射干酪乳杆菌细胞壁提取物（lactobacillus casei cell wall extract, LCWE）0.5 mL构建KD样血管炎小鼠模型，对照组腹腔注射等量的生理盐水。注射后第3天、第7天和第14天观察小鼠的一般情况。采用苏木精-伊红染色法观察冠状动脉组织病理学变化。采用酶联免疫吸附法检测小鼠血清中CHI3L1水平。采用免疫荧光染色法检测CHI3L1、血管性血友病因子（von Willebrand factor, vWF）、α-平滑肌肌动蛋白（α-smooth muscle actin, α-SMA）在冠状动脉组织中的表达及定位。采用Western blot法检测冠状动脉组织中CHI3L1、vWF、血管内皮钙黏蛋白（vascular endothelial cadherin, VE cadherin）、半胱天冬酶-3（Caspase-3）、B细胞淋巴瘤-2（B cell lymphoma-2, Bcl-2）、Bcl-2相关X蛋白（Bcl-2 associated X protein, Bax）、核转录因子κB（nuclear factor-κB, NF-κB）及磷酸化NF-κB（p-NF-κB）表达情况。结果模型组小鼠血清中CHI3L1含量较对照组明显升高（P<0.05）。与对照组相比，模型组小鼠冠状动脉组织中CHI3L1表达高于对照组，vWF表达低于对照组。模型组小鼠CHI3L1、Bax、Caspase-3、NF-κB及p-NF-κB蛋白相对表达量明显高于对照组（P<0.05）。模型组vWF、VE cadherin和Bcl-2蛋白相对表达量低于对照组（P<0.05）。结论 LCWE诱导的KD样血管炎小鼠模型中，血清及冠状动脉CHI3L1的表达水平升高，可能通过炎性反应介导血管内皮细胞凋亡在冠状动脉损伤中发挥作用。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	曹越
	高帅
	罗刚
	赵水炎
	唐雅琪
	杜占慧
	泮思林

关键词 ：川崎病, 壳多糖酶3样蛋白1, 血管炎, 冠状动脉损伤, 细胞凋亡, 小鼠

Abstract：Objective To explore the role and potential mechanisms of chitinase-3-like protein 1 (CHI3L1) in coronary artery lesions in a mouse model of Kawasaki disease (KD)-like vasculitis. Methods Four-week-old male SPF-grade C57BL/6 mice were randomly divided into a control group and a model group, with 10 mice in each group. The model group mice were intraperitoneally injected with 0.5 mL of lactobacillus casei cell wall extract (LCWE) to establish a mouse model of KD-like vasculitis, while the control group mice were injected with an equal volume of normal saline. The general conditions of the mice were observed on the 3rd, 7th, and 14th day after injection. Changes in coronary artery tissue pathology were observed using hematoxylin-eosin staining. The level of CHI3L1 in mouse serum was measured by enzyme-linked immunosorbent assay. Immunofluorescence staining was used to detect the expression and localization of CHI3L1, von Willebrand factor (vWF), and α-smooth muscle actin (α-SMA) in coronary artery tissue. Western blot analysis was used to detect the expression of CHI3L1, vWF, vascular endothelial cadherin (VE cadherin), Caspase-3, B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), nuclear factor κB (NF-κB), and phosphorylated NF-κB (p-NF-κB) in coronary artery tissue. Results The serum level of CHI3L1 in the model group was significantly higher than that in the control group (P<0.05). Compared to the control group, the expression of CHI3L1 in the coronary artery tissue was higher, while the expression of vWF was lower in the model group. The relative expression levels of CHI3L1, Bax, Caspase-3, NF-κB, and p-NF-κB were significantly higher in the model group than in the control group (P<0.05). The relative expression levels of vWF, VE cadherin, and Bcl-2 were lower in the model group than in the control group (P<0.05). Conclusions In the LCWE-induced mouse model of KD-like vasculitis, the expression levels of CHI3L1 in serum and coronary arteries increase, and it may play a role in coronary artery lesions through endothelial cell apoptosis mediated by inflammatory reactions.

Key words： Kawasaki disease Chitinase-3-like protein 1 Vasculitis Coronary artery lesion Apoptosis Mouse

收稿日期: 2023-09-15

基金资助:泰山学者工程资助（2018）。

通讯作者: 泮思林，男，主任医师，教授。Email：silinpan@126.com。 E-mail: silinpan@126.com

作者简介: 曹越，女，硕士研究生；

引用本文:

曹越,高帅,罗刚等. CHI3L1在川崎病样血管炎小鼠模型冠状动脉损伤中的作用及机制研究[J]. 中国当代儿科杂志, 2023, 25(12): 1227-1233.

CAO Yue,GAO Shuai,LUO Gang et al. Role and mechanisms of CHI3L1 in coronary artery lesions in a mouse model of Kawasaki disease-like vasculitis[J]. CJCP, 2023, 25(12): 1227-1233.

链接本文:

http://www.zgddek.com/CN/10.7499/j.issn.1008-8830.2309080 或 http://www.zgddek.com/CN/Y2023/V25/I12/1227

	Soni PR, Noval Rivas M, Arditi M. A comprehensive update on Kawasaki disease vasculitis and myocarditis[J]. Curr Rheumatol Rep, 2020, 22(2): 6. PMID: 32020498. DOI: 10.1007/s11926-020-0882-1.
	Rife E, Gedalia A. Kawasaki disease: an update[J]. Curr Rheumatol Rep, 2020, 22(10): 75. PMID: 32924089. PMCID: PMC7487199. DOI: 10.1007/s11926-020-00941-4.
	Gordon JB, Daniels LB, Kahn AM, et al. The spectrum of cardiovascular lesions requiring intervention in adults after Kawasaki disease[J]. JACC Cardiovasc Interv, 2016, 9(7): 687-696. PMID: 27056307. DOI: 10.1016/j.jcin.2015.12.011.
	Dichev V, Mehterov N, Kazakova M, et al. The lncRNAs/miR-30e/CHI3L1 axis is dysregulated in systemic sclerosis[J]. Biomedicines, 2022, 10(2): 496. PMID: 35203705. PMCID: PMC8962397. DOI: 10.3390/biomedicines10020496.
	Li F, Liu A, Zhao M, et al. Astrocytic chitinase-3-like protein 1 in neurological diseases: potential roles and future perspectives[J]. J Neurochem, 2023, 165(6): 772-790. PMID: 37026513. DOI: 10.1111/jnc.15824.
	ciborski K, Kuliczkowski W, Karolko B, et al. Plasma YKL-40 levels correlate with the severity of coronary atherosclerosis assessed with the SYNTAX score[J]. Pol Arch Intern Med, 2018, 128(11): 644-648. PMID: 30303489. DOI: 10.20452/pamw.4345.
	Jung YY, Kim KC, Park MH, et al. Atherosclerosis is exacerbated by chitinase-3-like-1 in amyloid precursor protein transgenic mice[J]. Theranostics, 2018, 8(3): 749-766. PMID: 29344304. PMCID: PMC5771091. DOI: 10.7150/thno.20183.
	Perumalsamy S, Huri HZ, Abdullah BM, et al. Genetic markers of insulin resistance and atherosclerosis in type 2 diabetes mellitus patients with coronary artery disease[J]. Metabolites, 2023, 13(3): 427. PMID: 36984867. PMCID: PMC10054456. DOI: 10.3390/metabo13030427.
	Suganuma E, Sato S, Honda S, et al. A novel mouse model of coronary stenosis mimicking Kawasaki disease induced by Lactobacillus casei cell wall extract[J]. Exp Anim, 2020, 69(2): 233-241. PMID: 31932543. PMCID: PMC7220718. DOI: 10.1538/expanim.19-0124.
	Hosseininasab A, Pashang F, Rukerd MRZ, et al. Kawasaki disease in children: a retrospective cross-sectional study[J]. Reumatologia, 2023, 61(3): 152-160. PMID: 37522144. PMCID: PMC10373172. DOI: 10.5114/reum/163170.
	McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association[J]. Circulation, 2017, 135(17): e927-e999. PMID: 28356445. DOI: 10.1161/CIR.0000000000000484.
	Zheng X, Li J, Yue P, et al. Is there an association between intravenous immunoglobulin resistance and coronary artery lesion in Kawasaki disease?-Current evidence based on a meta-analysis[J]. PLoS One, 2021, 16(3): e0248812. PMID: 33764989. PMCID: PMC7993784. DOI: 10.1371/journal.pone.0248812.
	Paniz-Mondolfi AE, van den Akker T, Márquez-Colmenarez MC, et al. Kawasaki disease seasonality in Venezuela supports an arbovirus infection trigger[J]. J Med Virol, 2020, 92(12): 2903-2910. PMID: 32740967. DOI: 10.1002/jmv.26381.
	Mazur M, Zielińska A, Grzybowski MM, et al. Chitinases and chitinase-like proteins as therapeutic targets in inflammatory diseases, with a special focus on inflammatory bowel diseases[J]. Int J Mol Sci, 2021, 22(13): 6966. PMID: 34203467. PMCID: PMC8268069. DOI: 10.3390/ijms22136966.
	Tizaoui K, Yang JW, Lee KH, et al. The role of YKL-40 in the pathogenesis of autoimmune diseases: a comprehensive review[J]. Int J Biol Sci, 2022, 18(9): 3731-3746. PMID: 35813465. PMCID: PMC9254466. DOI: 10.7150/ijbs.67587.
	Zhao T, Su Z, Li Y, et al. Chitinase-3 like-protein-1 function and its role in diseases[J]. Signal Transduct Target Ther, 2020, 5(1): 201. PMID: 32929074. PMCID: PMC7490424. DOI: 10.1038/s41392-020-00303-7.
	Kwon Y, Kim JH, Ha EK, et al. Serum YKL-40 levels are associated with the atherogenic index of plasma in children[J]. Mediators Inflamm, 2020, 2020: 8713908. PMID: 33061832. PMCID: PMC7533750. DOI: 10.1155/2020/8713908.
	Tsantilas P, Lao S, Wu Z, et al. Chitinase 3 like 1 is a regulator of smooth muscle cell physiology and atherosclerotic lesion stability[J]. Cardiovasc Res, 2021, 117(14): 2767-2780. PMID: 33471078. PMCID: PMC8848327. DOI: 10.1093/cvr/cvab014.
	van Sleen Y, Jiemy WF, Pringle S, et al. A distinct macrophage subset mediating tissue destruction and neovascularization in giant cell arteritis: implication of the YKL-40/interleukin-13 receptor α2 axis[J]. Arthritis Rheumatol, 2021, 73(12): 2327-2337. PMID: 34105308. PMCID: PMC9298326. DOI: 10.1002/art.41887.
	Noval Rivas M, Arditi M. Kawasaki disease: pathophysiology and insights from mouse models[J]. Nat Rev Rheumatol, 2020, 16(7): 391-405. PMID: 32457494. PMCID: PMC7250272. DOI: 10.1038/s41584-020-0426-0.
	Jia C, Zhuge Y, Zhang S, et al. IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway[J]. Cell Death Dis, 2021, 12(6): 575. PMID: 34083516. PMCID: PMC8174541. DOI: 10.1038/s41419-021-03852-z.
	Si F, Lu Y, Wen Y, et al. Cathelicidin (LL-37) causes expression of inflammatory factors in coronary artery endothelial cells of Kawasaki disease by activating TLR4-NF-κB-NLRP3 signaling[J]. Immun Inflamm Dis, 2023, 11(9): e1032. PMID: 37773705. PMCID: PMC10521377. DOI: 10.1002/iid3.1032.
	Zhao T, Zeng J, Xu Y, et al. Chitinase-3 like-protein-1 promotes glioma progression via the NF-κB signaling pathway and tumor microenvironment reprogramming[J]. Theranostics, 2022, 12(16): 6989-7008. PMID: 36276655. PMCID: PMC9576612. DOI: 10.7150/thno.75069.