Acetaldehyde dehydrogenase 2 (ALDH2) activated mitochondria preparation for treating myocardial ischemia reperfusion injury, and preparation method and application thereof

A technology for reperfusion injury and myocardial ischemia, applied in the field of biomedicine, can solve the problems of failing to exert cardioprotective effect and injury treatment effect, and achieve the effect of significant activation, excellent treatment effect and maintenance of vitality.

Active Publication Date: 2020-06-09
ZHONGSHAN HOSPITAL FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, there are literatures (McCully J D, Cowan D B, Pacak C A, etal. Injection of isolated mitochondria during early reperfusion forcardioprotection. Am J Physiol Heart Circ Physiol 2009, 296(1): H94~H105) showed that in the whole myocardial ischemia Injection of the ROS scavenger MPG

Method used

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  • Acetaldehyde dehydrogenase 2 (ALDH2) activated mitochondria preparation for treating myocardial ischemia reperfusion injury, and preparation method and application thereof
  • Acetaldehyde dehydrogenase 2 (ALDH2) activated mitochondria preparation for treating myocardial ischemia reperfusion injury, and preparation method and application thereof
  • Acetaldehyde dehydrogenase 2 (ALDH2) activated mitochondria preparation for treating myocardial ischemia reperfusion injury, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Technical route:

[0041] 1) Adult mouse cardiomyocytes were isolated, and 20 μM Alda-1 was intervened for 12 hours to activate the mitochondrial enzyme ALDH2.

[0042] 2) After performing Mitotracker red fluorescent labeling on the mitochondria of primary cardiomyocytes, the mitochondria of normal and ALDH2-activated cardiomyocytes were isolated for use.

[0043] 3) C57BL / 6 mice were anesthetized with gas, and the left anterior descending coronary artery was ligated to perform myocardial ischemia for 45 minutes, then the ligature was untied, and normal and ALDH2-activated mitochondria were transplanted into the left ventricular myocardium at multiple points, and reperfused for 24 hours at the same time.

[0044] 4) After 24 hours, the heart function of the mice with ischemia-reperfusion injury was detected, the location of mitochondria in cardiomyocytes was analyzed, the apoptosis level of ischemia-reperfusion myocardium before and after different mitochondria transpla...

Embodiment 2

[0062] At the same time as the above research, the following processing was done, and the supplementary content is as follows:

[0063] Intervention group 1: Mitochondrial transplantation after activation of IR+ALDH2, the difference from Example 1 is that the Alda-1 treatment time is 8 hours;

[0064] Intervention group 2: Mitochondrial transplantation after activation of IR+ALDH2, the difference from Example 1 is that the treatment time of Alda-1 is 10 h;

[0065] Intervention group 3: Mitochondrial transplantation after activation of IR+ALDH2, the difference from Example 1 is that the treatment time of Alda-1 is 14 hours;

[0066] Intervention group 4: Mitochondrial transplantation after activation of IR+ALDH2. The difference from Example 1 is that the mitochondria were directly extracted after isolation of cardiomyocytes, dissolved in PBS containing 20 μM Alda-1, and injected in the same way.

[0067] The statistical results of EF% and FS% of mice in each intervention grou...

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Abstract

The invention relates to an acetaldehyde dehydrogenase 2 (ALDH2) activated mitochondria preparation for treating myocardial ischemia reperfusion injury, and a preparation method and application thereof. According to the invention, ALDH2 in mitochondria of myocardial cells is activated by a small molecule activator Alda-1 for the first time, and the mitochondria of the myocardial cells are separated to carry out myocardial ischemia reperfusion injury transplantation. It is found that the mitochondria activated by the ALDH2 can remarkably increase productivity of the myocardial cells, reduce apoptosis of the myocardial cell after myocardial ischemia reperfusion injury, and improve myocardial ischemia reperfusion injury. Therefore, a mitochondrial preparation obtained by firstly carrying outtreatment by using Alda-1 after the myocardial cells are separated can enhance the treatment effect, so that transplantation of mitochondria activated by ALHD2 during revascularization of clinical acute myocardial infarction patients can guarantee myocardial energy supply, improve myocardial contraction and diastolic functions, reduce reperfusion injury, and inhibit occurrence of heart failure.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to an ALDH2-activated mitochondrial preparation for treating myocardial ischemia-reperfusion injury, a preparation method and application thereof. Background technique [0002] Ischemic cardiovascular diseases such as coronary heart disease and acute myocardial infarction are the most important killers threatening human health in the world today. Clinically, percutaneous coronary intervention to achieve timely vascular recanalization can effectively improve the myocardial function of patients. However, myocardial ischemia-reperfusion injury (ischemia and reperfusion, IR) occurs after patients receive revascularization therapy, which is nearly 10% of patients with acute myocardial infarction died within 1 year after discharge, and about 20% of surviving patients occurred Leading cause of chronic heart failure. There are a large number of mitochondria in cardiomyocytes to maintain the norm...

Claims

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Application Information

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IPC IPC(8): A61K35/34A61P9/10
CPCA61K35/34A61P9/10
Inventor 葛均波孙爱军孙晓垒高日峰李文佳
Owner ZHONGSHAN HOSPITAL FUDAN UNIV
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