中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (14): 2951-2957.doi: 10.12307/2025.611

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

有氧运动调节转化生长因子β/Smad通路缓解db/db糖尿病小鼠的肝脏纤维化

黄朝露1，黄  毅2，吴昌燕1，3，李芳菲1，李海燕4   

  1. 1黔东南民族职业技术学院临床医学系，贵州省凯里市  556000；2贵州医科大学基础医学院，贵州省贵阳市  550000；3贵州中医药大学基础医学院，贵州省贵阳市  550000；4温州医科大学附属第一医院康复科，浙江省温州市  325000
  • 收稿日期:2024-05-09 接受日期:2024-06-26 出版日期:2025-05-18 发布日期:2024-09-28
  • 通讯作者: 黄朝露，女，1994年生，贵州省铜仁市人，侗族，助教，主要从事肥胖或慢性病的康复研究。
  • 作者简介:李海燕，博士，主任医师，研究生导师，温州医科大学附属第一医院康复科，浙江省温州市 325000
  • 基金资助:
    国家自然科学基金资助项目(81501954)，项目负责人：李海燕；温州市科技局资助项目(Y2020053)，项目负责人：李海燕；黔东南民族职业技术学院院级资助项目(21zyyjyb05)，项目负责人：黄朝露

Aerobic exercise mitigates liver fibrosis in db/db diabetes mice by regulating transforming growth factor beta/Smad pathway

Huang Chaolu1, Huang Yi2, Wu Changyan1, 3, Li Fangfei1, Li Haiyan4   

  1. 1Department of Clinical Medicine, Qiandongnan Vocational and Technical College for Nationalities, Kaili 556000, Guizhou Province, China; 2School of Basic Medicine, Guizhou Medical University, Guiyang 550000, Guizhou Province, China; 3School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang 550000, Guizhou Province, China; 4Department of Rehabilitation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
  • Received:2024-05-09 Accepted:2024-06-26 Online:2025-05-18 Published:2024-09-28
  • Contact: Li Haiyan, PhD, Chief physician, Master’s supervisor, Department of Rehabilitation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
  • About author:Huang Chaolu, Assistant teacher, Department of Clinical Medicine, Qiandongnan Vocational and Technical College for Nationalities, Kaili 556000, Guizhou Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 81501954 (to LHY); Funded Project of Wenzhou Science and Technology Bureau, No. Y2020053 (to LHY); Funded Project of Qiandongnan Vocational and Technical College for Nationalities, No. 21zyyjyb05 (to HCL)

PDF

109

摘要：


文题释义：
肝纤维化：是指在慢性肝脏疾病发展的过程中，肝细胞被反复破坏后再生胶原、蛋白多糖等细胞外基质，在肝脏中弥漫性过度沉积与异常分布。
转化生长因子β/Smad信号通路：此信号通路参与了细胞生长、分化、凋亡、迁移、侵袭、细胞外基质产生等。转化生长因子β是纤维化和炎症发展的关键媒介，通过激活包括Smad2和Smad3在内的下游递质来发挥生物效应。

背景：有氧运动可抑制糖尿病小鼠肝纤维化，但具体作用机制尚未阐明。
目的：基于转化生长因子β/Smad信号通路探讨有氧运动改善db/db小鼠肝纤维化的作用机制。
方法：将8周龄雄性db/db小鼠和年龄匹配的m/m小鼠随机分为m/m对照组、m/m+运动组、db/db对照组、db/db+运动组，每组10只，运动组小鼠接受12周有氧运动。运动结束后检测各组小鼠空腹血糖，进行葡萄糖耐量测试和胰岛素耐量测试；摘取肝脏计算肝脏指数，摘眼球取血检测生化指标；苏木精-伊红染色、油红O染色和Masson染色观察小鼠肝组织的病理变化，免疫组化检测肝组织中转化生长因子β1、p-Smad3的表达；Western blot检测肝组织中转化生长因子β1、Smad3、p-Smad3、α-平滑肌肌动蛋白、Ⅰ型胶原蛋白和Ⅲ型胶原蛋白表达水平。
结果与结论：①与m/m组和m/m+运动组小鼠相比，db/db组小鼠体质量、肝质量、肝脏指数、空腹血糖、三酰甘油、总胆固醇、低密度脂蛋白和肌酶水平均显著升高(P < 0.01)；高密度脂蛋白水平显著降低(P < 0.01)；转化生长因子β1、p-Smad3、α-平滑肌肌动蛋白、Ⅰ型胶原蛋白和Ⅲ型胶原蛋白表达水平显著升高(P < 0.01)；葡萄糖、胰岛素耐量测试的曲线下面积显著增加(P < 0.01)；肝组织病理染色显示大量炎症细胞浸润，脂滴增多，明显纤维化；②与db/db组相比，db/db+运动组小鼠体质量、肝质量、肝脏指数、空腹血糖、三酰甘油、总胆固醇、低密度脂蛋白和肌酶水平显著降低(P < 0.05或P < 0.01)；高密度脂蛋白水平显著升高(P < 0.05)；转化生长因子β1、p-Smad3、α-平滑肌肌动蛋白、Ⅰ型胶原蛋白和Ⅲ型胶原蛋白表达显著降低(P < 0.05或P < 0.01)；此外，糖耐量、胰岛素耐量测试的曲线下面积明显减少(P < 0.01，P < 0.05)，肝脏病理损伤得到明显改善；③结果表明，有氧运动有效减轻了糖尿病小鼠肝纤维化，其机制可能与调控转化生长因子β/Smad信号通路有关。
https://orcid.org/0000-0002-8684-9624(黄朝露)

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: 有氧运动, 转化生长因子β, Smad, 信号通路, db/db, 肝纤维化

Abstract: BACKGROUND: Aerobic exercise can suppress liver fibrosis in diabetic mice. However, the specific mechanism is yet to be elucidated.
OBJECTIVE: To investigate the protective effect and mechanism of aerobic exercise on liver fibrosis in db/db mice via the transforming growth factor-β/Smad signaling pathway. 
METHODS: 8-week-old male db/db mice and age-matched m/m mice were randomly divided into m/m control group, m/m+exercise group, db/db control group, and db/db+exercise group, with 10 mice in each group. Mice in the exercise group were subjected to a 12-week aerobic exercise. After the exercise, fasting blood glucose levels were measured in mice, and glucose tolerance and insulin tolerance tests were conducted. Mouse liver was extracted to calculate liver index and mouse eyeballs were taken to collect blood sample and detect biochemical indicators. Masson, oil red O and Hematoxylin-eosin staining were used to detect and analyze the pathological changes in mouse liver tissues. Immunohistochemistry was used to determine the protein expression levels of transforming growth factor-β1 and p-Smad3. Western blot analysis was applied to determine the protein expression levels of transforming growth factor-β1, Smad3, p-Smad3, α-smooth muscle actin, type I collagen and type III collagen.

RESULTS AND CONCLUSION: Compared with the m/m group and m/m+exercise group, body mass, liver mass, liver index, fasting blood glucose, triglycerides, total cholesterol, low-density lipoprotein and creatine kinase levels were significantly increased (P < 0.01), but the high-density lipoprotein level significantly decreased (P < 0.01) in the db/db group; the protein expressions of transforming growth factor-β1, p-Smad3, α-smooth muscle actin, type I collagen and type III collagen significantly increased (P < 0.01) in the db/db group; the area under curve of glucose and insulin tolerance tests significantly increased (P < 0.01) in the db/db group; and pathological staining of the liver in the db/db group showed extensive infiltration of inflammatory cells, increased lipid droplets, and significant fibrosis. In the db/db+exercise group, aerobic exercise could significantly reduce body mass, liver mass, liver index, fasting blood glucose, triglycerides, total cholesterol, low-density lipoprotein and creatine kinase levels (P < 0.05 or P < 0.01), and increase high-density lipoprotein level (P < 0.05). Similarly, a marked decrease was observed in the protein expression levels of transforming growth factor-β1, p-Smad3, α-smooth muscle actin, type I collagen and type III collagen (P < 0.05 or P < 0.01) in the db/db+exercise group. In addition, the area under the curve of glucose tolerance and insulin tolerance tests significantly decreased (P < 0.01, P < 0.05), and pathological changes in liver tissues were significantly improved. In conclusion, aerobic exercise can attenuate liver fibrosis in diabetic mice, which may be related to the regulation of the transforming growth factor-β1/Smad signaling pathway.

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: aerobic exercise, transforming growth factor-β, Smad, signaling pathway, db/db, liver fibrosis

中图分类号: