中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (30): 6441-6448.doi: 10.12307/2025.780

• 组织构建实验造模 experimental modeling in tissue construction • 上一篇    下一篇

有氧运动对CNPY2基因调控AKT/GSK3β通路改善非酒精性脂肪肝的作用研究

王佳倩1，2，蒋昌君3，彭  毅4，马  咪4，李军汉2   

  1. 1龙岩学院体育与健康学院，福建省龙岩市  346012；2成都体育学院运动医学与健康学院，四川省成都市  610041；3西南石油大学体育学院，四川省成都市  610041；4莆田学院体育学院，福建省莆田市  351100
  • 收稿日期:2024-08-14 接受日期:2024-10-31 出版日期:2025-10-28 发布日期:2025-03-27
  • 通讯作者: 李军汉，博士，教授，成都体育学院运动医学与健康学院，四川省成都市 610041
  • 作者简介:王佳倩，女，1997年生，福建省莆田市人，汉族，2022年成都体育学院毕业，硕士，主要从事运动干预与健康促进的研究。
  • 基金资助:
    国家自然科学基金青年基金资助项目(31900846)，项目负责人：李军汉；四川省科技厅自然科学基金资助面上项目(2024NSFSC0644)，项目负责人：李军汉

Study on the role of aerobic exercise in regulating the CNPY2-mediated AKT/GSK3β pathway for improving non-alcoholic fatty liver 

Wang Jiaqian1, 2, Jiang Changjun3, Peng Yi4, Ma Mi4, Li Junhan2   

  1. 1School of Physical Education and Health, Longyan University, Longyan 346012, Fujian Province, China; 2School of Sports Medicine and Health, Chengdu Sport University, Chengdu 610041, Sichuan Province, China; 3School of Physical Education, Southwest University of Petroleum, Chengdu 610041, Sichuan Province, China; 4School of Physical Education, Putian University, Putian 351100, Fujian Province, China
  • Received:2024-08-14 Accepted:2024-10-31 Online:2025-10-28 Published:2025-03-27
  • Contact: Li Junhan, PhD, Professor, School of Sports Medicine and Health, Chengdu Sport University, Chengdu 610041, Sichuan Province, China
  • About author:Wang Jiaqian, MS, School of Physical Education and Health, Longyan University, Longyan 346012, Fujian Province, China; School of Sports Medicine and Health, Chengdu Sport University, Chengdu 610041, Sichuan Province, China
  • Supported by:
    National Natural Science Foundation of China (Youth Fund Project), No. 31900846 (to LJH); Natural Science Foundation Project of Sichuan Provincial Science and Technology Department, No. 2024NSFSC0644 (to LJH) 

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摘要：


文题释义：
冠层FGF信号调节器2(Canopy FGF signaling regulator 2，CNPY2)：是一种新型血管生成生长因子，广泛表达于哺乳动物身体的各种组织和器官中，尤其是在心脏、肺和肝脏中 。CNPY2可以通过促进血管生成参与肿瘤的发展；在心血管疾病中促进细胞增殖和组织修复，改善心脏功能，在神经系统疾病中增强神经突生长。
细胞凋亡：是细胞对环境的生理性和/或病理性的刺激性信号，它涉及一系列基因的刺激、表达及调控等作用，凋亡可被多种信号激活，如钙稳态失调、氧化损伤、线粒体损伤等，是为更好地适应生存环境而主动争取的一种死亡过程。

背景：非酒精性脂肪肝是全球常见慢性肝病之一，有氧运动被认为是非酒精性脂肪肝治疗的重要手段，然而，运动改善非酒精性脂肪肝的机制尚未完全明确。
目的：旨在探讨有氧运动对非酒精性脂肪肝小鼠肝脏CNPY2介导蛋白激酶B/糖原合成酶激酶3β通路的影响及作用机制。
方法：雄性CNPY2基因敲除小鼠(ko)及其同系同窝野生型小鼠(wt)各30只，适应性喂养1周，随机分为对照组、模型组和模型运动组，每组10只。对照组予普通饲料喂养，模型组和模型运动组予高脂饲料喂养，连续17 周；模型运动组从第10 周开始进行连续有氧运动干预，直至第18 周实验结束。苏木精-伊红染色和油红O染色观察小鼠肝组织病理学形态；全自动生化仪检测小鼠血清血脂4项及肝功能水平；Western Blot法检测肝组织CNPY2、蛋白激酶B/糖原合成酶激酶3β通路、半胱天冬酶3(Caspase-3)蛋白发表达水平；TUNEL染色检测肝细胞凋亡率。
结果与结论：①与wt对照组比较，wt模型组肝组织CNPY2表达升高(P < 0.05)，与wt模型组比较，wt模型运动组CNPY2表达下降(P < 0.05)；与对照组比较，wt小鼠与ko小鼠对应的模型组肝细胞脂肪变性、脂滴增多、血脂及肝功能异常，肝组织蛋白激酶B/糖原合成酶激酶3β表达下降(P < 0.05)、Caspase-3表达升高(P < 0.05)，肝细胞凋亡率增加(P < 0.05)；②与模型组比较，wt小鼠与ko小鼠对应的模型运动组上述指标均有所改善；③与wt小鼠比较，ko小鼠对应组上述指标均有所改善；④结果说明，CNPY2基因缺失和有氧运动可有效改善非酒精性脂肪肝，其机制可能与有氧运动降低CNPY2表达、激活蛋白激酶B/糖原合成酶激酶3β信号通路，进而抑制肝细胞凋亡有关。

https://orcid.org/0009-0003-2505-614X(王佳倩)

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

关键词: 脂肪肝, 高脂饮食, 肝细胞凋亡, 有氧运动, CNPY2, AKT, GSK3β, Caspase-3

Abstract: BACKGROUND: Non-alcoholic fatty liver disease is one of the common chronic liver diseases in the world. Aerobic exercise is considered to be an important means for the treatment of non-alcoholic fatty liver disease. However, the mechanism of exercise to improve non-alcoholic fatty liver disease has not been fully clarified.
OBJECTIVE: To investigate the effects of aerobic exercise on the protein kinase B/glycogen synthase kinase-3β pathway mediated by Canopy FGF signaling regulator 2 (CNPY2) in the liver canopy of non-alcoholic fatty liver disease mice and its mechanism.
METHODS: Thirty male CNPY2 knockout mice (ko) and thirty their litters of wild-type mice (wt) were fed adaptively for one week and randomly divided into control group, model group, and model exercise group, with 10 mice in each group. The control group was fed with ordinary diet. The model group and the model exercise group were fed with high-fat diet for 17 weeks. The model exercise group received continuous aerobic exercise intervention from week 10 until the end of the experiment at week 18. Liver histopathology was observed by hematoxylin-eosin and oil red O staining. The levels of serum lipids and liver function were detected by automatic biochemical analyzer. The expression levels of CNPY2, protein kinase B/glycogen synthase kinase-3β pathway, and Caspase-3 protein in liver tissues were detected by Western Blotting. The apoptosis rate of hepatocytes was detected by TUNEL staining. 
RESULTS AND CONCLUSION: (1) Compared with wt control group, CNPY2 expression in liver tissues of wt model group was increased (P < 0.05), while CNPY2 expression in wt model exercise group was decreased compared with wt model group (P < 0.05). Compared with control group, wt mice and ko mice in model group showed steatosis, increased lipid droplets, abnormal blood lipids and liver function, decreased protein kinase B/glycogen synthase kinase-3β expression 
(P < 0.05) and increased Caspase-3 expression (P < 0.05), and increased hepatocyte apoptosis rate in liver tissue (P < 0.05). (2) Compared with the model group, wt mice and ko mice showed improvement in the above indexes in model exercise group. (3) Compared with wt mice, the above indexes of ko mice were improved. (4) These findings indicate that CNPY2 gene deletion and aerobic exercise can effectively improve non-alcoholic fatty liver disease. The mechanism may be related to aerobic exercise reducing CNPY2 expression, activating protein kinase B/glycogen synthase kinase-3β signaling pathway, and thus inhibiting hepatocyte apoptosis.  

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: fatty liver, high-fat diet, hepatocyte apoptosis, aerobic exercise, CNPY2, AKT, GSK3β, Caspase-3

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