中国组织工程研究 ›› 2024, Vol. 28 ›› Issue (34): 5508-5515.doi: 10.12307/2024.841

• 组织构建细胞学实验 cytology experiments in tissue construction • 上一篇    下一篇

有氧运动上调硫氧还蛋白系统抑制衰老大鼠心肌细胞凋亡

徐  政1,赵晓琴1,陈肖丹1,王嘉璞2,鲍粉苗1,于  亮3,李俊平3,魏  延2   

  1. 太原理工大学,1体育学院,2生物医学工程学院,山西省太原市  030024;3北京体育大学运动人体科学学院,北京市  100084
  • 收稿日期:2023-11-20 接受日期:2024-01-16 出版日期:2024-12-08 发布日期:2024-03-14
  • 通讯作者: 赵晓琴,副教授,太原理工大学体育学院,山西省太原市 030024
  • 作者简介:徐政,男,1999年生,辽宁省锦州市人,满族,太原理工大学在读硕士,主要从事运动训练和运动生理方面的研究。
  • 基金资助:
    国家自然科学基金项目(32071168),项目参与人:于亮;中央高校基本科研业务费专项资金资助项目(2022YB019),项目负责人:于亮;山西省自然科学基金面上项目(201901D111079),项目负责人:赵晓琴

Aerobic exercise upregulates the thioredoxin system and inhibits cardiomyocyte apoptosis in aging rats

Xu Zheng1, Zhao Xiaoqin1, Chen Xiaodan1, Wang Jiapu2, Bao Fenmiao1, Yu Liang3, Li Junping3, Wei Yan2   

  1. 1School of Physical Education, 2School of Biomedical Engineering, Taiyuan University of Technology, Taiyuan 030024, Shanxi Province, China; 3School of Sports Human Science, Beijing Sport University, Beijing 100084, China
  • Received:2023-11-20 Accepted:2024-01-16 Online:2024-12-08 Published:2024-03-14
  • Contact: Zhao Xiaoqin, Associate professor, School of Physical Education, Taiyuan University of Technology, Taiyuan 030024, Shanxi Province, China
  • About author:Xu Zheng, Master candidate, School of Physical Education, Taiyuan University of Technology, Taiyuan 030024, Shanxi Province, China
  • Supported by:
    the National Natural Science Foundation of China, No. 32071168 (to YL [project participant]); the Fundamental Research Funds for the Central Universities, No. 2022YB019 (to YL); the Natural Science Foundation of Shanxi Province (General Program), No. 201901D111079 (to ZXQ)

摘要:


文题释义:

细胞凋亡:是多细胞生物体发生的程序性细胞死亡形式,它负责组织重塑、正常细胞更新以及免疫系统的发育和功能。
有氧运动:是以中低强度的长时间持续运动为主,并且主要以有氧代谢作为供应以支持肌肉运动的方式,对增强免疫能力、预防及改善心血管疾病、糖尿病等慢性疾病均具有显著效果。


背景:研究表明,心肌细胞凋亡与心脏功能减退及心脏衰老过程密切相关,适宜的运动可以改变心力衰竭患者的心泵功能以及减轻衰老引起的心肌细胞凋亡、肥大和纤维化损伤。

目的:探究长期有氧运动对衰老大鼠心肌细胞凋亡及硫氧还蛋白系统的影响。
方法:选取雄性SD大鼠36只,按照鼠龄分为青年组(3月龄)、中年组(9月龄)、老年组(18月龄),每组12只;每组又分为安静、运动2个亚组,每组6只,安静组常规饲养,运动组进行有氧运动训练(45 min/d,5 d/周,训练10周)。末次训练后24 h,采用ELISA法检测大鼠血清肌钙蛋白Ⅰ和血清肌酸激酶同工酶MB水平,TUNEL染色检测心肌细胞凋亡,Western Blot检测大鼠心肌组织中Bax、Bcl-2、Caspase 3、硫氧还蛋白1、硫氧还蛋白2、硫氧还蛋白还原酶1、硫氧还蛋白还原酶2、硫氧还蛋白相互作用蛋白、凋亡信号调节激酶1、P38丝裂原活化激酶的蛋白表达。

结果与结论:①老年安静组大鼠血清肌钙蛋白Ⅰ和肌酸激酶同工酶MB水平高于青年安静组、中年安静组、老年运动组(P < 0.01),老年运动组大鼠血清肌钙蛋白Ⅰ和肌酸激酶同工酶MB水平高于青年运动组、中年运动组(P < 0.01);②无论是安静状态还是运动训练后,随着鼠龄的增加,大鼠凋亡心肌细胞数量及Bax、Caspase 3蛋白表达逐渐升高,Bcl-2蛋白表达逐渐降低;与同龄段安静组相比,运动组大鼠凋亡心肌细胞数量及Bax、Caspase 3蛋白表达均不同程度降低,Bcl-2蛋白表达均不同程度升高;③老年安静组大鼠心肌硫氧还蛋白1、硫氧还蛋白2、硫氧还蛋白还原酶1、硫氧还蛋白还原酶2蛋白表达低于青年安静组、中年安静组、老年运动组(P < 0.05,P < 0.01);老年运动组大鼠心肌硫氧还蛋白1、硫氧还蛋白2、硫氧还蛋白还原酶2蛋白表达低于青年运动组(P < 0.05,P < 0.01),硫氧还蛋白还原酶1、硫氧还蛋白还原酶2蛋白表达低于中年运动组(P < 0.01);④老年安静组大鼠心肌硫氧还蛋白相互作用蛋白、凋亡信号调节激酶1、P38丝裂原活化激酶蛋白表达高于青年安静组、中年安静组、老年运动组(P < 0.01),老年运动组大鼠心肌硫氧还蛋白相互作用蛋白、凋亡信号调节激酶1、P38丝裂原活化激酶蛋白表达高于青年运动组、中年运动组(P < 0.01);⑤结果表明,有氧运动可能通过下调硫氧还蛋白相互作用蛋白表达来增强硫氧还蛋白的表达,下调凋亡信号调节激酶1及P38丝裂原活化激酶蛋白的表达,从而减轻衰老大鼠心肌细胞的凋亡。

https://orcid.org/0009-0003-1767-7851(徐政)

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, 衰老大鼠, 心肌细胞, 细胞凋亡, 硫氧还蛋白

Abstract: BACKGROUND: Studies have shown that cardiomyocyte apoptosis is closely related to cardiac decompensation and the cardiac aging process. Appropriate exercise can alter heart pump function in patients with heart failure as well as attenuate aging-induced cardiomyocyte apoptosis, hypertrophy, and fibrotic damage.
OBJECTIVE: To investigate the effects of long-term aerobic exercise on cardiomyocyte apoptosis and the thioredoxin system in aging rats.
METHODS: Thirty-six male Sprague-Dawley rats were selected and divided into three age groups: 3-month-old young group, 9-month-old middle-aged group, and 18-month-old elderly group, with 12 rats in each group. Within each age group, rats were randomly assigned to sedentary and exercise subgroups (n=6 per group). The sedentary groups did not undergo any exercise intervention. The exercise groups were acclimated to a treadmill environment and subsequently subjected to treadmill exercise for 45 minutes per day, at a speed of 15 m/min, 5 days per week for 10 weeks in total. At 24 hours after the final intervention, ELISA was employed to measure serum levels of cardiac troponin I and creatine kinase-MB in rats. TUNEL assay was utilized to detect cardiomyocyte apoptosis, while western blot assay was employed to assess the protein expression of Bax, Bcl-2, Caspase 3, thioredoxin-1, thioredoxin-2, thioredoxin reductase-1, thioredoxin reductase-2, thioredoxin-interacting protein, apoptosis signal-regulating kinase 1, and P38 mitogen-activated protein kinase in rat myocardial tissue.
RESULTS AND CONCLUSION: Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged sedentary groups and elderly exercise group (P < 0.01). Serum levels of cardiac troponin I and creatine kinase-MB in the elderly sedentary group were significantly higher than those in the young and middle-aged exercise groups and elderly exercise group (P < 0.01). Positive apoptotic cells in rat myocardial tissue, along with increased protein expression of Bax and Caspase 3, exhibited an age-related upward trend, while Bcl-2 protein expression showed a declining trend. In comparison with the sedentary groups within each age category, the number of apoptotic cardiomyocytes and the expression of Bax and Caspase 3 proteins were reduced to different degrees, and the expression of Bcl-2 protein was increased to different degrees in the corresponding exercise groups. Compared with the young sedentary group, middle-aged sedentary group and elderly exercise group, elderly sedentary rats showed a significant decrease in the expression of myocardial thioredoxin 1, thioredoxin 2, thioredoxin reductase 1, and thioredoxin reductase 2 proteins (P < 0.05, P < 0.01). The expression of myocardial thioredoxin 1, thioredoxin 2, and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the young exercise group (P < 0.05, P < 0.01), while the expression of thioredoxin reductase 1 and thioredoxin reductase 2 proteins was lower in the elderly exercise group than in the middle-aged exercise group (P < 0.01). The protein expression of thioredoxin-interacting protein, apoptosis signal-regulating kinase 1, and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly sedentary group than the young sedentary group, middle-aged sedentary group and elderly exercise group (P < 0.01). The protein expression of thioredoxin-interacting protein, apoptosis signal-regulating kinase 1, and P38 mitogen-activated protein kinase in rat myocardium was significantly higher in the elderly exercise group than the young exercise group and middle-aged exercise group (P < 0.01). To conclude, aerobic exercise may enhance the anti-apoptotic effects of thioredoxin by down-regulating the expression of thioredoxin-interacting protein in aging rat hearts, leading to the downregulation of apoptosis signal-regulated kinase 1 and P38 mitogen-activated kinase protein, thereby alleviating myocardial cell apoptosis in aging rat hearts.

Key words: aerobic exercise, aging rat, cardiomyocyte, apoptosis, thioredoxin

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