| Akt-Kv4.3-CaMKⅡ在有氧运动抑制压力负荷小鼠
心肌肥厚中的作用及其机制 |
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| 引用本文： | 葛广全,赵峰,陈道虎,石振塑,陈泽伦,王天光,何书武,魏以桢.Akt-Kv4.3-CaMKⅡ在有氧运动抑制压力负荷小鼠
心肌肥厚中的作用及其机制[J].天津医药,2020,48(1):38-44. |
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| 作者姓名： | 葛广全 赵峰 陈道虎 石振塑 陈泽伦 王天光 何书武 魏以桢 |
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| 作者单位： | 基金项目：海南省卫生厅科研课题（1521320273A2001）
作者单位：1海口，海南医学院第二附属医院心血管外科（邮编570311）；2武汉，华中科技大学同济医学院附属协和医院外科；3北京，中国
医学科学院阜外医院外科
作者简介：葛广全（1972），男，本科，副主任医师，主要从事心衰及心梗发病机制研究
△通讯作者 E-mail: weiyizhen@sohu.com |
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| 摘 要： | 目的 探讨丝氨酸/苏氨酸激酶（Akt）-离子通道Kv4.3（Kv4.3）-钙调素依赖性蛋白激酶Ⅱ（CaMKⅡ）信号
通路在有氧运动抑制压力负荷小鼠心肌肥厚中的作用及其机制。方法 60只实验小鼠均分为5组：假手术（SHAM）
组、主动脉缩窄手术（TAC）组、假手术+有氧运动（SHAM+E）组、主动脉缩窄术+有氧运动（TAC+E）组，主动脉缩窄术+
有氧运动+ Akt抑制剂Perifosine（TAC+E+Peri）组。高分辨率小动物超声系统评价小鼠心功能及肥厚程度，麦胚凝集
素（WGA）染色检测心肌细胞横截面积；荧光定量PCR（RT-qPCR）检测ANP表达，Western blot检测蛋白心房钠尿肽
（ANP）、p-Akt、Kv4.3、p-CaMKⅡ表达水平。结果 与SHAM组相比，TAC促进心肌肥厚，恶化心功能（P＜0.01）。给
予有氧运动训练后，TAC+E组较TAC组小鼠心功能改善，心肌肥厚程度减轻（P＜0.01）。同时Western blot检测显示，
TAC组较SHAM组p-Akt、Kv4.3表达降低，p-CaMKⅡ上调（P＜0.01）；TAC+E组p-Akt和Kv4.3表达较TAC小鼠增加，
p-CaMKⅡ下调（P＜0.01）。而给予Akt抑制剂Perifosine后，相比于TAC+E组，TAC+E+Peri组心功能恶化、心肌肥厚
程度和ANP表达增加，心肌细胞横截面积增大，同时伴随Kv4.3表达降低、p-CaMKⅡ增高（P＜0.01）。结论 有氧运
动训练能够通过调节Akt-Kv4.3-CaMKⅡ信号通路抑制压力负荷心肌肥厚。
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| 关 键 词： | 心肌病 肥厚性 蛋白质丝氨酸苏氨酸激酶 钙-钙调素依赖性蛋白激酶2型 疾病模型 动物 有氧运动 离子通道Kv4.3 |
| 收稿时间： | 2019-01-25 |
| 修稿时间： | 2019-07-22 |
The role and mechanism of Akt-Kv4.3-CaMKII in aerobic exercise inhibited pressure
overload-induced cardiac hypertrophy |
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| GE Guang-quan,ZHAO Feng,CHEN Dao-hu,SHI Zhen-su,CHEN Ze-lun,WANG Tian-guang,HE Shu-wu,WEI Yi-zhen.The role and mechanism of Akt-Kv4.3-CaMKII in aerobic exercise inhibited pressure
overload-induced cardiac hypertrophy[J].Tianjin Medical Journal,2020,48(1):38-44. |
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| Authors: | GE Guang-quan ZHAO Feng CHEN Dao-hu SHI Zhen-su CHEN Ze-lun WANG Tian-guang HE Shu-wu WEI Yi-zhen |
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| Affiliation: | 1 Department of Cardiovascular Surgery, the Second Affiliated Hospital, Hainan Medical College, Haikou 570311, China;
2 Department of Hand Surgery, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and
Technology; 3 Department of Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences
△Corresponding Author E-mail: weiyizhen@sohu.com |
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| Abstract: | Objective To investigate the role and mechanism of serine / threonine kinase (Akt) - ion channel Kv4.3
(Kv4.3) - calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ) signaling pathway in aerobic exercise inhibited pressure
overload-induced cardiac hypertrophy. Methods Sixty mice were divided into five groups: Sham group, transverse aortic
constriction (TAC) group, SHAM+ aerobic exercise (E) group, TAC + E group and TAC+ E + AKt inhibitor perifosine (Peri)
group. Transthoracic echocardiography was used to assess the cardiac function and extent of myocardial hypertrophy. The
cross-sectional area of myocardial cells was measured by WGA staining. The mRNA expression of ANP was detected by RTqPCR. The protein expression levels of ANP, p-AKt, Kv4.3 and p-CaMKⅡ were detected by Western-blot assay. Results
Compared with Sham group, the cardiac function of mice was deteriorated in TAC group (P＜0.01), and the extent of cardiac
hypertrophy was increased (P＜0.01). After aerobic exercise training, the cardiac function was improved in TAC + E group,
and the level of myocardial hypertrophy was alleviated compared with TAC group (P＜0.01). Western-blot assay showed that
the expressions of p-AKT and Kv4.3 were down-regulated, p-CaMKⅡ was up-regulated in TAC group than those in Sham group (P＜0.01). However, the expressions of p-AKT and Kv4.3 were higher, p-CaMKⅡ was lower in TAC+E group than
those in TAC mice (P＜0.01). Furthermore, pretreatment with the AKT inhibitor perifosine, deteriorated cardiac function,
augmented myocardial hypertrophy and ANP, increased cross-sectional area were observed in TAC+E+Peri group compared
with those of TAC+E group (P＜0.01). Meanwhile, the downregulation of p-AKT、Kv4.3 and upregulation p-CaMKⅡ were
detected in the TAC+E+Peri group compared with the TAC+E group. Conclusion Aerobic exercise training can inhibit
pressure overload-induced cardiac hypertrophy by regulating Akt-Kv4.3-CaMKⅡ. |
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| Keywords: | cardiomyopathy hypertrophic protein-serine-threonine kinases calcium-calmodulin-dependent protein kinase type 2 disease models animal aerobic exercise Kv4 3 |
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