mdivi-1对急性心肌缺血小鼠心脏的保护作用

李清晖; 吴跃; 匡磊; 李涛

doi:10.16016/j.1000-5404.202102056

您当前的位置：

首页 >

文章列表页 >

mdivi-1对急性心肌缺血小鼠心脏的保护作用

基础医学 | 更新时间：2026-01-09

- mdivi-1对急性心肌缺血小鼠心脏的保护作用
- Protective effect of mdivi-1 on heart of mice after acute myocardial ischemia
- 第三军医大学学报 2021年43卷第14期页码：1326-1331
- 作者机构：
  
  400042 重庆，陆军特色医学中心野战外科研究部战伤休克与输血研究室，创伤、烧伤与复合伤国家重点实验室
- 作者简介：
  
  [ 李涛，E-mail: LT200132@163.com LI Tao, E-mail: LT200132@163.com
- 基金信息：
  
  国家自然科学基金重点项目(81730059)
- DOI：10.16016/j.1000-5404.202102056
  中图分类号： R-332;R542.2;R977.6
- 收稿：2021-02-08，
  
  修回：2021-04-12，
  
  纸质出版：2021-07-30
- 稿件说明：
移动端阅览
李清晖, 吴跃, 匡磊, 等. mdivi-1对急性心肌缺血小鼠心脏的保护作用[J]. 第三军医大学学报, 2021,43(14):1326-1331.

Qinghui LI, Yue WU, Lei KUANG, et al. Protective effect of mdivi-1 on heart of mice after acute myocardial ischemia[J]. Journal of Third Military Medical University, 2021, 43(14): 1326-1331.
李清晖, 吴跃, 匡磊, 等. mdivi-1对急性心肌缺血小鼠心脏的保护作用[J]. 第三军医大学学报, 2021,43(14):1326-1331. DOI： 10.16016/j.1000-5404.202102056.

Qinghui LI, Yue WU, Lei KUANG, et al. Protective effect of mdivi-1 on heart of mice after acute myocardial ischemia[J]. Journal of Third Military Medical University, 2021, 43(14): 1326-1331. DOI： 10.16016/j.1000-5404.202102056.

摘要

目的

观察线粒体分裂抑制剂mdivi-1对缺血小鼠心肌的保护作用。

方法

采用结扎心脏左前降支制作小鼠急性心肌缺血模型，将140只C57小鼠按随机数表分成4组，每组35只: 假手术组(只穿线不结扎)，假手术+mdivi-1组(穿线不结扎同时尾静脉注射mdivi-1)，缺血组(结扎心脏左前降支制作急性心肌缺血模型)，mdivi-1组(结扎心脏左前降支并尾静脉注射mdivi-1)。通过测定SOD、MDA、ATP、ROS、心肌损伤标志物并对心肌及细胞线粒体进行形态学观察，研究mdivi-1对心肌缺血小鼠心脏的保护作用。

结果

缺血后小鼠心肌结构显著受损且线粒体碎片化程度增高，排列紊乱，线粒体功能显著受损，表现为线粒体分裂抑制剂mdivi-1能显著减轻心肌线粒体结构及功能损伤，缺血心肌细胞周围损伤带缩窄、心肌ATP(1.587±0.227)μmol/mg和SOD(0.401±0.138)U/mg含量显著上升(

0.05)，ROS(4 276.0±687.5)荧光强度/mg和MDA(3.538±1.110)μmol/mg含量显著下降(

0.05)，降低心肌氧化损伤、心肌损伤标志物水平，保护心肌功能，显著延长模型小鼠存活时间，提高存活率。

结论

线粒体分裂抑制剂mdivi-1对心肌缺血小鼠心脏有保护作用。

Abstract

Objective

To observe the protective effect of mdivi-1

a mitochondrial fission inhibitor

on mice after myocardial ischemia.

Methods

A total of 140 C57 mice were randomly divided into 4 groups (

=35)

that is

Sham group

Sham+mdivi-1 group

ischemia group

and mdivi-1 group. Mouse model of acute myocardial ischemia was established by ligating left anterior descending branch in mice. SOD

MDA

ATP

ROS and markers of myocardial injury were measured

and myocardial and mitochorial morphology was observed to study the protective effect of mdivi-1 on the he

art of myocardial ischemia mice.

Results

The mice in the ischemia group showed damaged myocardial structure

more mitochondrial fragmentation

disordered arrangement

and obviously impaired mitochondrial function. While the treatment of mdivi-1 significantly reduced above damaged mitochondrial structure and function in myocardial cells

restored myocardial ATP (1.587±0.227 μmol/mg) and SOD (0.401±0.138 U/mg) contents (

0.05)

and decreased the production of ROS (4 276.0±687.5 fluorescent intensity/mg) and content of MDA (3.538±1.110 μmol/mg) (

0.05)

and thus alleviated the oxidative damages in the myocardium

reduced the levels of blood markers of myocardial injury

protected myocardial function

and finally significantly prolonged the survival time and improved the survival rate of myocardial ischemia mice.

Conclusion

Mitochondrial fission inhibitor mdivi-1 has a protective effect on myocardial ischemia mice.

关键词

Keywords

references

PASCUAL-GIL S, GARBAYO E, DÍAZ-HERRÁEZ P, et al . Heart regeneration after myocardial infarction using synthetic biomaterials[J ] . J Control Release, 2015, 203: 23-38. DOI:10.1016/j.jconrel.2015.02.009.

O'GARA P T, KUSHNER F G, ASCHEIM D D, et al . 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the American College of Emergency Physicians and Society for Cardiovascular Angiography and Interventions[J ] . Catheter Cardiovasc Interv, 2013, 82(1): E1-E27. DOI:10.1002/ccd.24776.

IBANEZ B, JAMES S, AGEWALL S, et al . 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC)[J ] . Eur Heart J, 2018, 39(2): 119-177. DOI:10.1093/eurheartj/ehx393.

LI J, LI X, WANG Q, et al . ST-segment elevation myocardial infarction in China from 2001 to 2011 (the China PEACE-Retrospective Acute Myocardial Infarction Study): a retrospective analysis of hospital data[J ] . Lancet, 2015, 385(9966): 441-451. DOI:10.1016/S0140-673 6(14)60921-1.

ROSSELLÓ X, HUO Y, POCOCK S, et al . Global geographical variations in ST-segment elevation myocardial infarction management and post-discharge mortality[J ] . Int J Cardiol, 2017, 245: 27-34. DOI:10.1016/j.ijcard.2017.07.039.

林春, 陈关海, 吴柱国. 急性心肌梗死预后的影响因素[J]. 海南医学, 2020, 31(2): 227-230.

LIN C, CHEN G H, WU Z G. Prognostic factors of acute myocardial infarction[J]. Hainan Med J, 2020, 31(2): 227-230.

薛大忠, 赵自刚, 牛春雨. 线粒体损伤及其在心肌细胞损伤中的作用[J]. 中国老年学杂志, 2016, 36(1): 223-227. DOI:10.3969/j.issn.1005-9202.2016.01.103.

XUE D Z, ZHAO Z G, NIU C Y. Mitochondrial damage and its role in myocardial cell injury[J]. Chin J Gerontol, 2016, 36(1): 223-227. DOI:10.3969/j.issn.1005-9202.2016.01.103.

赵丽, 周巧霞, 王拴, 等. 线粒体分裂和融合相关蛋白质的研究进展[J]. 生理学报, 2018, 70(4): 424-432. DOI:10.13294/j.aps.2018.0054.

ZHAO L, ZHOU Q X, WANG S, et al . Research progress of mitochondrial fission and fusion related proteins[J ] . Acta Physiol Sin, 2018, 70(4): 424-432. DOI:10.13294/j.aps.2018.0054.

DUAN C Y, WANG L, ZHANG J, et al . Mdivi-1 attenuates oxidative stress and exerts vascular protection in ischemic/hypoxic injury by a mechanism independent of Drp1 GTPase activity[J ] . Redox Biol, 2020, 37: 101706. DOI:10.1016/j.redox.2020.101706.

GAO E, LEI Y H, SHANG X, et al . A novel and efficient model of coronary artery ligation and myocardial infarction in the mouse[J ] . Circ Res, 2010, 107(12): 1445-1453. DOI:10.1161/circresaha.110.223925.

SUN T T, ZHANG L H, LI X X, et al . MicroRNA-1 and circulating microvesicles mediate the protective effects of dantonic in acute myocardial infarction rat models[J ] . Front Physiol, 2018, 9: 664. DOI:10.3389/fphys.2018.00664.

DAVIDSON S M, ARJUN S, BASALAY M V, et al . The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection-evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology[J ] . Basic Res Cardiol, 2018, 113(6): 43. DOI:10.1007/s00395-018-0704-z.

任静娜, 马宏昕, 饶本龙, 等. 大鼠心肌细胞急性分离方法及影响因素探讨[J]. 中西医结合心脑血管病杂志, 2018, 16(8): 1034-1037.

REN J N, MA H X, RAO B L, et al . Acute isolation of cardiomyocy tes in rat and its influencing factors[J ] . Chin J Integr Med Cardio-/Cerebrovasc Dis, 2018, 16(8): 1034-1037.

钟敏, 宁竹之, 石凯, 等. 锻炼与药物复合处理对模拟高原低氧下小鼠心肌线粒体作用的图象分析[J]. 解放军预防医学杂志, 1996, 14(6): 402-404.

ZHONG M, NING Z Z, SHI K, et al . Image analysis of the effects of the combination use of training and drug intervention on myocardlal mitochondria in mice[J ] . J Prev Med Chin PLA, 1996, 14(6): 402-404.

YANG T F, ZHANG X F, MA C M, et al . TGF-β/Smad3 pathway enhances the cardio-protection of S1R/SIPR1 in in vitro ischemia-reperfusion myocardial cell model[J ] . Exp Ther Med, 2018, 16(1): 178-184. DOI:10.3892/etm.2018.6192..

JANAHMADI Z, NEKOOEIAN A A, MOAREF A R, et al . Oleuropein offers cardioprotection in rats with acute myocardial infarction[J ] . Cardiovasc Toxicol, 2015, 15(1): 61-68. DOI:10.1007/s12012-014-9271-1.

YU B, ZHANG G, AN Y, et al . Morroniside on anti-inflammation activities in rats following acute myocardial infarction[J ] . Korean J Physiol Pharmacol, 2018, 22(1): 17-21. DOI:10.4196/kjpp.2018.22.1.17.

SHANMUGAM K, RAVINDRAN S, KURIAN G A, et al . Fisetin confers cardioprotection against myocardial ischemia reperfusion injury by suppressing mitochondrial oxidative stress and mitochondrial dysfunction and inhibiting glycogen synthase kinase 3β activity[J ] . Oxid Med Cell Longev, 2018, 2018: 9173436. DOI:10.1155/2018/9173436.

ELGASS K, PAKAY J, RYAN M T, et al . Recent advances into the understanding of mitochondrial fission[J ] . Biochim Biophys Acta, 2013, 1833(1): 150-161. DOI:10.1016/j.bbamcr.2012.05.002.

ZHANG Z Z, LIU L, WU S N, et al . Drp1, Mff, Fis1, and MiD51 are coordinated to mediate mitochondrial fission during UV irradiation-induced apoptosis[J ] . Faseb J, 2016, 30(1): 466-476. DOI:10.1096/fj.15-274258.

CHEN Y, LIN J R, GAO P J. Mitochondrial division inhibitor Mdivi-1 ameliorates angiotensin Ⅱ-induced endothelial dysfunction[J]. Acta Physiol Sin, 2016, 68(5): 669-676.

李献帅, 穆军升. 线粒体融合蛋白1、线粒体融合蛋白2与心肌细胞生理机能关系的研究进展[J]. 中国胸心血管外科临床杂志, 2013, 20(4): 457-462.

LI X S, MU J S. Research progress of relationship between mitochondrial fusion protein 1, mitochondrial fusion protein 2 and physiological function of cardiomyocyte[J]. Chin J Clin Thorac Cardiovasc Surg, 2013, 20(4): 457-462.

LEES J G, KONGA M, CHEN Y C, et al . Mitochondrial fusion by M1 promotes embryoid body cardiac differentiation of human pluripotent stem cells[J ] . Stem Cells Int, 2019, 2019: 6380135. DOI:10.1155/2019/6380135.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

抑制线粒体分裂通过改善微循环及血管通透性保护爆炸失血性休克大鼠的多器官功能

Mdivi-1通过抑制过度线粒体自噬改善低氧复合丙泊酚引起的未成熟SD大鼠认知功能障碍

线粒体分裂抑制剂Mdivi-1对高原战创伤休克大鼠的保护作用

莱菔硫烷对肝细胞的抗氧化能力和线粒体功能的影响

PGC-1α通过线粒体介导巨噬细胞极化状态的机制研究