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miR-1改善异丙肾上腺素诱导的小鼠心力衰竭
Intravenous delivery of a microRNA-1 agomir improves isoproterenol-induced heart failure in mice
- 第三军医大学学报 2019年41卷第14期 页码：1357-1364
- 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：
DOI：10.16016/j.1000-5404.201901040
中图分类号： Q522.2;R-332;R541.605收稿：2019-01-06，
修回：2019-01-30，
纸质出版：2019-07-30
- 稿件说明：
移动端阅览
何芮, 丁畅, 何丽, 等. miR-1改善异丙肾上腺素诱导的小鼠心力衰竭[J]. 第三军医大学学报, 2019,41(14):1357-1364.
Rui HE, Chang DING, Li HE, et al. Intravenous delivery of a microRNA-1 agomir improves isoproterenol-induced heart failure in mice[J]. Journal of Third Military Medical University, 2019, 41(14): 1357-1364.
何芮, 丁畅, 何丽, 等. miR-1改善异丙肾上腺素诱导的小鼠心力衰竭[J]. 第三军医大学学报, 2019,41(14):1357-1364. DOI： 10.16016/j.1000-5404.201901040.
Rui HE, Chang DING, Li HE, et al. Intravenous delivery of a microRNA-1 agomir improves isoproterenol-induced heart failure in mice[J]. Journal of Third Military Medical University, 2019, 41(14): 1357-1364. DOI： 10.16016/j.1000-5404.201901040.
摘要
目的
2
探讨miR-1对异丙肾上腺素(isoproterenol
ISO)诱导的小鼠心力衰竭的作用。
方法
2
60 mg/kg ISO连续腹腔注射28 d建立C57BL/6小鼠心力衰竭模型，生理盐水连续腹腔注射28 d作为对照，第29天行超声心动图评估心力衰竭模型。模型建立后对miR-1治疗组、模型组和对照组分别予以agomir-1、agomir对照试剂和生理盐水尾静脉注射，2次/周，第7天再次行超声心动图检查，取小鼠心脏组织行HE染色、天狼星红染色、Masson三色染色、WGA及Ki67免疫荧光染色。酶联免疫法检测血清NT-proBNP水平。Western blot检测与免疫组化染色评估miR-1靶基因线粒体钙单向转运蛋白(mitochondrial calcium uniporter，MCU)的表达。
结果
2
ISO连续腹腔注射28 d成功建立小鼠心力衰竭模型。超声心动图检测结果显示，miR-1治疗组小鼠心功能较模型组明显改善(
P
<
0.05)；组织学观察结果显示，miR-1治疗组小鼠心肌排列紊乱、心肌纤维化、心肌细胞肥大及细胞增殖等心室重构情况较模型组明显改善。miR-1治疗组血清NT-proBNP水平较模型组明显下降(
P
<
0.05)，但仍高于对照组(
P
<
0.05)。Western blot检测与免疫组化结果显示，miR-1治疗组小鼠MCU的表达较模型组明显减少(
P
<
0.05)。
结论
2
输注miR-1可能通过调节MCU的表达来改善ISO诱导的小鼠心力衰竭。
Abstract
Objective
2
To investigate the therapeutic effect of intravenous administration of a microRNA-1 (miR-1) agomir on isoproterenol (ISO)-induced heart failure (HF) in mice.
Methods
2
Mouse models of HF were established by intraperitoneal injection of ISO for 28 consecutive days at a daily dose of 60 mg/kg
and the control mice were injected with normal saline in the same manner. The success of modeling was verified by echocardiography on the next day after completion of the injections. On days 1 and 4 after successful modeling
the mice were received injections of a miR-1 agomir (miR-1 group) or a control agomir (model group)
via
the tail vein; the control mice were injected with normal saline only. The 3 groups of mice were again subjected to echocardiography on day 7. At the end of the experiment
the mice were sacrificed for assessing ventricular remodeling using HE staining
Sirius Red staining
WGA staining and Ki67 assay; the levels of serum NT-proBNP were detected using enzyme-linked immunosorbent assay
and the expression of mitochondrial calcium uniporter (MCU
the target gene of miR-1) in the cardiac tissues was detected with Western blotting and immunohistochemical staining.
Results
2
The HF model was successfully established by intraperitoneal injections of ISO for 28 consecutive days. Intravenous administration of the miR-1 agomir significantly improved cardiac function and ventricular remodeling. Compared with that in the model group
the serum level of NT-proBNP in the HF models was significantly lowered following treatment with the miR-1 agomir
but still remained higher than that in the control group (
P
<
0.05). The results of Western blotting and immunohistochemistry demonstrated a significant reduction of the expression of MCU in the cardiac tissues of miR-1-treated mice (
P
<
0.05).
Conclusion
2
Intravenous injection of the miR-1 agomir can improve ISO-induced HF in mice probably by modulating MCU expression in the cardiac tissues.
关键词
Keywords
references
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