Urantide调控Wnt/β连环蛋白信号通路减轻ApoE-/-动脉粥样硬化小鼠心肌损伤

HUANG  Hui1; LENG  Ze-hua2; SONG  He3; WANG  Tu1; CUI  Hai-peng1; ZOU  Run1; CUI  Bin-yan1; ZHAO  Juan1*(1.Department of Pathophysiology; Chengde Medical University; Hebei Chengde 067000

doi:10.16098/j.issn.0529-1356.2026.02.011

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解剖学报 ›› 2026, Vol. 57 ›› Issue (2) : 237-244. DOI: 10.16098/j.issn.0529-1356.2026.02.011

组织学胚胎学发育生物学

Urantide调控Wnt/β连环蛋白信号通路减轻ApoE^-/-动脉粥样硬化小鼠心肌损伤

黄慧¹吝泽华²宋贺³王途¹崔海鹏¹邹润¹崔彬彦¹赵娟^1*

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Urantide modulating the Wnt/β-catenin signaling pathway to alleviate myocardial injury in ApoE^-/-atherosclerosis mice

HUANG Hui¹, LENG Ze-hua², SONG He³, WANG Tu¹, CUI Hai-peng¹, ZOU Run¹, CUI Bin-yan¹, ZHAO Juan^1*

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摘要

目的探讨urantide调节尾加压素Ⅱ（UⅡ）/UⅡ受体(UT)系统和Wnt/β连环蛋白（β-cat）信号通路对ApoE^-/-动脉粥样硬化(AS)小鼠心肌损伤的影响。方法将ApoE^-/-小鼠随机分为模型组、辛伐他汀组和urantide低、中、高剂量组(n=12)，同时取12只C57BL/6小鼠作为正常对照组。HE和Masson三色染色法观察ApoE^-/-小鼠心肌组织病理学变化；免疫组织化学染色检测心脏组织中UⅡ和G蛋白耦联受体14（GPR14）的表达；免疫荧光染色检测 β-cat蛋白表达；Western blotting 检测 ApoE^-/-小鼠心肌组织中Wnt-3a、β-cat及蛋白质降解复合体［糖原合成酶激酶-3β(GSK-3β)、p-GSK-3β、活化蛋白C (APC)、轴抑制蛋白2(Axin-2)、酪蛋白激酶1α(CK-1α）］表达水平。结果模型组小鼠心肌组织出现水肿、炎性细胞浸润及胶原沉积等典型病理变化，UⅡ、GPR14、Wnt-3a、β-cat和p-GSK-3β蛋白水平升高，CK-1α、Axin-2、APC、GSK-3β明显降低（P<0.05）；与模型组相比，urantide组小鼠心肌组织病理损伤程度显著缓解，UⅡ、GPR14、Wnt-3a、β-cat和p-GSK-3β蛋白水平降低，CK-1α、Axin-2、APC、GSK-3β明显升高（P<0.05）。结论 Urantide通过调控UⅡ/UT系统和Wnt/β-cat信号通路减轻ApoE^-/-AS小鼠心肌损伤。

Abstract

Objective To investigate the effects of urantide on myocardial injury in ApoE^-/- mice by regulating the urotensin Ⅱ(UⅡ)/urotensin II receptor (UT) system and the Wnt/β-catenin(β-cat) signaling pathway. Methods ApoE^-/- atherosclerotic(AS) mice were randomly divided into the model group, simvastatin group, and urantide low dose group, urantide medium dose group, and urantide high-dose urantide groups (n=12 per group), while 12 C57BL/6 mice were used as the normal control group. Myocardial histopathological changes were observed using HE and Masson’s trichrome staining. Immunohistochemistry was performed to detect UⅡ and G protein couple receptor 14 (GPR14) protein expression in cardiac tissues, while immunofluorescent staining was used to assess β-cat expression. Western blotting was employed to measure the expression levels of Wnt-3a, β-cat, and components of the β-catenin degradation complex, glycogen synthase kinase-3β(GSK-3β), p-GSK-3β, activity protein C (APC), axis inhibition protein-2(Axin-2), and casein kinase-1α(CK-1α) in myocardial tissues. Results The model group exhibited typical pathological changes, including myocardial edema, inflammatory cell infiltration, and collagen deposition. Protein levels of UⅡ, GPR14, Wnt-3a, β-cat, and p-GSK-3β increased significantly, while CK-1α, Axin-2, APC, and GSK-3β decreased markedly(P<0.05). Compared with the model group, the urantide treatment group showed significant alleviation of myocardial injury, along with reduced expression of UⅡ, GPR14, Wnt-3a, β-cat, and p-GSK-3β, and increased levels of CK-1α, Axin-2, APC, and GSK-3β (P<0.05). Conclusion Urantide mitigates myocardial injury in ApoE^-/- atherosclerotic mice by modulating the UⅡ/UT system and the Wnt/β-cat signaling pathway.

关键词

动脉粥样硬化 / Wnt/β连环蛋白信号通路 / 心肌损伤 / Urantide / 免疫荧光 / 免疫印迹法 / ApoE-/-小鼠

Key words

Atherosclerosis

/ Wnt/β-catenin signaling pathway / Myocardial injury / Urantide / Immunofluorescence / Western blotting / ApoE^-/-mouse

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黄慧吝泽华宋贺王途崔海鹏邹润崔彬彦赵娟. Urantide调控Wnt/β连环蛋白信号通路减轻ApoE^-/-动脉粥样硬化小鼠心肌损伤[J]. 解剖学报. 2026, 57(2): 237-244 https://doi.org/10.16098/j.issn.0529-1356.2026.02.011

HUANG Hui, LENG Ze-hua, SONG He, WANG Tu, CUI Hai-peng, ZOU Run, CUI Bin-yan, ZHAO Juan. Urantide modulating the Wnt/β-catenin signaling pathway to alleviate myocardial injury in ApoE^-/-atherosclerosis mice[J]. Acta Anatomica Sinica. 2026, 57(2): 237-244 https://doi.org/10.16098/j.issn.0529-1356.2026.02.011

中图分类号： R363

参考文献

［1］ Zhang YZh, Shang Q, Ren H, et al. ‘Heart-Bone’ axis theory based pathological mechanisms elucidating of myocardial infarction and osteoporosis［J/OL］. Chinese Journal of Experimental Formulas.https://doi.org/10.13422/j.cnki.syfjx.20251136. (in Chinese)

张玉卓,尚奇,任辉,等.基于“心-骨”轴理论探讨心肌梗死和骨质疏松症的病理机制［J/OL］.中国实验方剂学杂志. https://doi.org/10.13422/j.cnki.syfjx.20251136.

［2］ Huo BX, Jia HX, Ning YZh. Research progress of cognitive function decline in patients with coronary heart disease［J］. Journal of Capital Medical University, 2025,43(3):496-502. (in Chinese)

霍碧岫,贾竑晓,宁艳哲.冠状动脉动脉粥样硬化性心脏病患者认知功能下降的研究进展［J］.首都医科大学学报, 2025,43(3):496-502.

［3］ Zhang NN, Xu HY, Liu XN, et al. The inhibitory role of hydrogen sulfide in UⅡ-induced cardiovascular effects and the underlying signaling pathways［J］. Antioxidants (Basel), 2022,11(11):2253.

［4］ Zhou R, Li L, Liu X, et al.Research progress of urotensin Ⅱ and urotensin Ⅱ receptor［J］. Acta Pharmaceutica Sinica,2016, 51(05): 684-689. (in Chinese)

周睿,李莉,刘旭,等.尾加压素Ⅱ及其受体的研究进展［J］.药学学报,2016,51(05):684-689.

［5］ Yu Q, Wei P, Xu L, et al. Urotensin Ⅱ Enhances Advanced Aortic Atherosclerosis Formation and Delays Plaque Regression in Hyperlipidemic Rabbits［J］. Int J Mol Sci. 2023;24(4):3819.

［6］ Li YL, Li L, Zhang ShY. The role of Wnt/β-catenin pathway in atherosclerosis［J］. Chinese Journal of Cardiovascular Research, 2022, 20(6): 503-507. (in Chinese)

李亚兰,黎莉,张韶英.Wnt/β-catenin通路在动脉粥样硬化发生中的作用［J］.中国心血管病研究,2022,20(6):503-507.

［7］ Wang M, Que WX, Chen GL. Simvastatin prevents cerebral ischemia-reperfusion injury and regulates clock genes in hyperlipidemia mice［J］. Chinese Journal of Pharmacology and Toxicology, 2024, 38(7):496-503. (in Chinese)

王敏,阙文轩,陈刚领.辛伐他汀预防小鼠高脂血症合并脑缺血损伤及其对时钟基因的调控［J］.中国药理学与毒理学杂志,2024,38(7):496-503.

［8］ Wang QQ, Zhang DSh, Gao J, et al. High-resolution magnetic resonance imaging studies of stroke recurrence in patients with symptomatic atherosclerotic middle cerebral artery occlusion ［J］. Journal of Clinical Radiology, 2025, 44(2): 220-225. (in Chinese)

王倩倩, 张东升, 高洁, 等.症状性动脉粥样硬化性大脑中动脉闭塞患者卒中复发的高分辨率磁共振成像研究［J］.临床放射学杂志,2025,44(2):220-225.

［9］ Lü SJ, Wu ShL, Zhu ChR, et al. Predictive value of atherogenic index of plasma for acute myocardial infarction［J］. Chinese Journal of Cardiology, 2024, 29(1): 40-45. (in Chinese)

吕素洁,吴寿岭,朱辰蕊,等.血浆致动脉粥样硬化指数对急性心肌梗死发生的预测价值［J］.中国心血管杂志,2024,29(1):40-45.

［10］ Kong Q, Ma X, Li L, et al. Atherosclerosis burden of brain- and heart-supplying arteries and the relationship with vascular risk in patients with ischemic stroke［J］. J Am Heart Assoc, 2023, 12(16):e029505.

［11］ Gonzalez-Domínguez A, Tormo JR, Herrería-Bustillo VJ. Aortic thrombosis and acute kidney injury due to atherosclerosis in a dog［J］. J Am Vet Med Assoc, 2024, 262(8):1-4.

［12］ Zhou XD, Tian N, Zheng MH. Excerpt of an international multidisciplinary consensus statement on MAFLD and the risk of CVD(2023)［J］. Journal of Clinical Hepatology, 2023, 39(10): 2336-2339. (in Chinese)

周晓东,田娜,郑明华.《2023年国际多学科专家共识：代谢相关脂肪性肝病和心血管疾病风险》摘译［J］. 临床肝胆病杂志,2023,39(10):2336-2339.

［13］ Ajoolabady A, Pratico D, Lin L, et al. Inflammation in atherosclerosis: pathophysiology and mechanisms［J］. Cell Death Dis, 2024,15(11):817.

［14］ Shah PK. Inflammation, infection and atherosclerosis［J］. Trends Cardiovasc Med, 2019,29(8):468-472.

［15］ Libby P. Inflammation and the pathogenesis of atherosclerosis［J］. Vascul Pharmacol,2024,154:107255.

［16］ Zhi XM, Zhang J, Lu D, et al. Effects and mechanism of urotensin Ⅱ on the expression of oxidative stress/endoplasmic reticulum stress on high glucose-stimulated cardiomyocytes［J］. Chinese Journal of Circulation, 2021, 36(1): 80-85. (in Chinese)

支杏敏,张捷,卢东,等.尾加压素Ⅱ在高糖诱导心肌细胞氧化应激、内质网应激中的作用及机制研究［J］.中国循环杂志,2021,36(1):80-85.

［17］ Hayat R, Manzoor M, Hussain A. Wnt signaling pathway: a comprehensive review［J］. Cell Biol Int, 2022,46(6):863-877.

［18］ Obianom ON, Ai Y, Li Y, et al. Triazole-based inhibitors of the Wnt/β-catenin signaling pathway improve glucose and lipid metabolisms in diet-induced obese mice［J］. J Med Chem, 2019,62(2):727-741.

［19］ Zhao Y, Wang C, Hong X, et al. Wnt/β-catenin signaling mediates both heart and kidney injury in type 2 cardiorenal syndrome［J］. Kidney Int, 2019, 95(4):815-829.

［20］ Zhang X, Huang Z, Fan X, et al. Molecular mechanisms and effects of urocortin II on rat adventitial fibroblast calcification induced by calcified medium［J］. Vasc Biol, 2022,4(1):19-27.