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miR-669a-5p通过AMPK/PGC1α信号通路改善心力衰竭小鼠心肌细胞能量代谢
MiR-669a-5p improves cardiomyocyte energy metabolism
via AMPK/PGC1α signaling pathway in mice with heart failure- 陆军军医大学学报 2024年46卷第1期 页码：84-90
- 作者机构：
1.400014 重庆，重庆医科大学附属第二医院心血管内科
2.610041 成都，四川大学华西医院病理研究室
- 作者简介：
[苏立，E-mail: sulicq@163.com SU Li, E-mail: sulicq@163.com
- 基金信息：国家自然科学基金面上项目(81974036)
DOI：10.16016/j.2097-0927.202303160
中图分类号： R322.11;R363.25;R541.6收稿：2023-03-27，
修回：2023-05-18，
纸质出版：2024-01-15
- 稿件说明：
移动端阅览
蔡明茗, 周双珊, 刘源, 等. miR-669a-5p通过AMPK/PGC1α信号通路改善心力衰竭小鼠心肌细胞能量代谢[J]. 陆军军医大学学报, 2024,46(1):84-90.
Mingming CAI, Shuangshan ZHOU, Yuan LIU, et al. MiR-669a-5p improves cardiomyocyte energy metabolism
via AMPK/PGC1α signaling pathway in mice with heart failure[J]. Journal of Army Medical University, 2024, 46(1): 84-90.蔡明茗, 周双珊, 刘源, 等. miR-669a-5p通过AMPK/PGC1α信号通路改善心力衰竭小鼠心肌细胞能量代谢[J]. 陆军军医大学学报, 2024,46(1):84-90. DOI： 10.16016/j.2097-0927.202303160.
Mingming CAI, Shuangshan ZHOU, Yuan LIU, et al. MiR-669a-5p improves cardiomyocyte energy metabolism
via AMPK/PGC1α signaling pathway in mice with heart failure[J]. Journal of Army Medical University, 2024, 46(1): 84-90. DOI： 10.16016/j.2097-0927.202303160.
摘要
目的
2
探讨主动脉弓缩窄(transverse aortic constriction，TAC)诱导的小鼠衰竭心肌中miR-669a-5p的表达变化，并进一步研究miR-669a-5p对心力衰竭小鼠的作用及可能机制。
方法
2
将24只小鼠按随机数字表法分为假手术组(Sham组，
n
＝8)和手术组(
n
=16，建立TAC心力衰竭模型)。TAC术后第4周将手术组随机分为模型组(TAC组，
n
=8)及miR-669a-5p agomir组(Agomir组，
n
=8)，Sham组、TAC组及Agomir组连续4周尾静脉分别注射生理盐水、agomir阴性对照试剂及agomir试剂，2次/周。第8周行超声心动图评估各组小鼠心功能；HE、天狼星红及WGA免疫荧光染色观察小鼠心肌组织病理学变化。RT-qPCR检测小鼠心肌组织miR-669a-5p及氧化磷酸化相关基因(
ND1
、
ND2
、
NDUFA4
、
ATP5O
)的表达。ATP检测试剂盒检测各组心肌组织ATP浓度。Western blot检测心肌组织p-AMPK、AMPK、PGC-1α蛋白表达水平变化。
结果
2
与Sham组比较，TAC组小鼠心肌miR-669a-5p表达显著减少(
P
＜0.05)。超声检测结果显示：Agomir组小鼠心脏射血能力、收缩与舒张功能较TAC组明
显改善(
P
＜0.05)。组织切片染色显示：与TAC组比较，Agomir组可见心肌细胞排列紊乱、心肌纤维化及心肌细胞横截面积等有明显改善(
P
＜0.05)。与TAC组比较，Agomir组ATP水平较TAC组明显升高(
P
＜0.05)，且
ND1
、
ND2
、
NDUFA4
、
ATP5O
基因相对表达量均显著升高(
P
＜0.05)。Agomir组小鼠心肌组织p-AMPK/AMPK、PGC1α蛋白水平表达较TAC组显著增加(
P
＜0.05)。
结论
2
miR-669a-5p可以显著改善主动脉弓缩窄诱导的心力衰竭小鼠心功能及心室重构，其机制可能是通过调控AMPK/PGC1α信号通路进而改善小鼠心肌细胞能量代谢。
Abstract
Objective
2
To investigate the change in expression of microRNA-669a-5p (miR-669a-5p) in mice with heart failure (HF) induced by transverse aortic constriction (TAC) and to further explore the role and possible mechanism of miR-669a-5p in HF mice.
Methods
2
Twenty-four mice were randomly divided into the sham surgery group (Sham group
n
=8) and the surgery group (
n
=16
TAC induced HF model). In the 4th week after TAC surgery
the mice from the surgery group was randomized into the model group (TAC group
n
=8) and miR-669a-5p agomir group (Agomir group
n
=8). Normal saline
agomir negative control and agomir reagent were respectively injected
via
tail vein into the corresponding groups
twice a week for 4 weeks. In the 8th week after TAC
the cardiac function of each group was measured by echocardiography. HE
Sirius red and WGA staining were used to observe the pathological changes in the myocardium tissues. The expression of miR-669a-5p and oxidative phosphorylation related genes (
ND1
ND2
NDUFA
4 and
ATP5O
) were detected by RT-qPCR. The ATP content of myocardial tissues in each group was measured by ATP assay kit. The protein levels of AMPK
p-AMPK and PGC-1α were detected by Western blotting.
Results
2
The expression of miR-
669a-5p was significantly decreased in the TAC group compared with the Sham group (
P
<
0.05). Compared with those in the TAC group
echocardiography showed that the Agomir group significantly improved cardiac function (
P
<
0.05)
as well as histopathological analysis suggested that the Agomir group significantly improved cardiac remodeling (
P
<
0.05). The ATP levels in the Agomir group were significantly higher than that in the TAC group (
P
<
0.05)
and the mRNA levels of
ND1
ND2
NDUFA4
and
ATP5O
were dramatically higher (
P
<
0.05). Western blotting showed that the protein levels of p-AMPK/AMPK and PGC1α were significantly up-regulated in the Agomir group compared with the TAC group (
P
<
0.05).
Conclusion
2
MiR-669a-5p significantly improves cardiac function and cardiac remodeling in mice with TAC-induced HF
and the mechanism may be associated with the up-regulation of AMPK/PGC1α signaling pathway and further improvement of myocardial energy metabolism in mice.
关键词
Keywords
references
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