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Application of melatonin in promotion of cardiac stem cell transplanting for treating myocardial infarction

A myocardial infarction and stem cell technology, applied in the field of medicine, can solve the problems of lack of donor sources, improve myocardial blood supply problems, high costs, etc., and achieve the effects of reducing mortality, increasing cardioprotection, and increasing therapeutic effects

Inactive Publication Date: 2018-06-26
HARBIN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although these methods can relieve vascular obstruction, relieve ventricular remodeling, and improve the deterioration of cardiac function and the occurrence of arrhythmia, they cannot reverse myocardial necrosis and regenerate infarcted myocardial cells.
Heart transplantation is one of the treatment methods for many serious heart diseases including myocardial infarction, but it is difficult to be widely used clinically due to reasons such as lack of donor sources, transplant rejection, failure of transplanted tissue, and high cost.
For the treatment of myocardial infarction, the above treatment methods still have problems in improving myocardial blood supply and heart function

Method used

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  • Application of melatonin in promotion of cardiac stem cell transplanting for treating myocardial infarction
  • Application of melatonin in promotion of cardiac stem cell transplanting for treating myocardial infarction
  • Application of melatonin in promotion of cardiac stem cell transplanting for treating myocardial infarction

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1: Melatonin promotes the proliferation of CPCs damaged by oxidative stress and inhibits apoptosis

[0026] 1 Experimental method

[0027] 1.1 Cell proliferation was detected by EdU staining, cell apoptosis was detected by Tunel staining

[0028] By culturing cardiac stem cells (CPCs) in vitro, CPCs were pretreated with different concentrations of melatonin, and 150 μM H was added after 2 h. 2 o 2 Make the cells in the state of oxidative stress-induced damage, according to whether or not to give H 2 o 2 and the different experiments of melatonin concentration were divided into 7 groups: control group (CTL), H 2 o 2 , H 2 o 2 +Mel(10nM),H 2 o 2 +Mel(100nM), H 2 o 2 +Mel (1μM), H 2 o 2 +Mel (10μM), H 2 o 2 +Mel (100 μM). After 24 hours of treatment, EdU staining was used to detect the effect of melatonin on the proliferation of CPCs.

[0029] 1.2 Experimental group design

[0030] According to whether to give H 2 o 2 and the different experimen...

Embodiment 2

[0036] Example 2: Melatonin promotes the therapeutic effect of myocardial stem cell transplantation on myocardial infarction in mice

[0037] 1 Experimental method

[0038] 1.1B Ultrasound Doppler Instrument to Detect Cardiac Function in Mice

[0039] After in vitro culture of CPCs, CPCs were treated with 10 μM melatonin for 2 hours, and the treated CPCs or untreated CPCs were injected into the surrounding tissue of myocardial infarction mice in the form of point injection. After 4 weeks, B-mode ultrasonic Doppler The heart function of the mouse was detected by a Le instrument, and left ventricular end-diastolic diameter (left ventricular internal diastolic diameter, LVIDd), left ventricular end-systolic internal diameter (left ventricular internal dimension at end-systole, LVIDs), left ventricular end-diastolic volume (left ventricular end diastolic volume, LV vold), left ventricular end-systolic volume (left ventricular end-systolic volume, LV vol s), cardiac ejection fract...

Embodiment 3

[0047] Example 3: The protective effect of melatonin on CPCs is dependent on melatonin membrane receptors

[0048] 1 Experimental method

[0049] 1.1 EdU staining was used to detect the proliferation ability of CPCs, and Tunel staining was used to detect the apoptosis level of CPCs

[0050] CPCs cells were cultured in vitro, and were divided into oxidative stress groups according to different treatment methods (H 2 o 2 ), melatonin-treated oxidative stress group (H 2 o 2 +Mel), the oxidative stress group treated with melatonin and luzindole (H 2 o 2 +Mel+L). Oxidative stress group (H 2 o 2 ) Add 150 μM H to the cultured CPCs 2 o 2 , melatonin-treated oxidative stress group (H 2 o 2 +Mel) Add 150 μM H to the cultured CPCs 2 o 2 and 10 μM melatonin, the oxidative stress group treated with melatonin and luzindole (H 2 o 2 +Mel+L) Add 10 μM melatonin membrane receptor luzindole (L) to the cultured CPCs cells to treat CPCs, then add 150 μM H 2 o 2 and 10 μM melato...

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Abstract

The invention discloses application of melatonin in promotion of cardiac stem cell transplanting for treating myocardial infarction. The application is characterized in that by performing in-vitro culture on cardiac stem cells (CPCs), the CPCs are pretreated for 2h by the melatonin of different concentrations, and then 150muM H2O2 (hydrogen peroxide) is lately added to simulate the oxidative stress loss of cells; after 24h, an Edu dyeing is used for detecting the influence of the melatonin to the cell proliferation of the CPCs, and a Tunnel experiment is used for detecting the cell withering;in addition, the CPCs are cultured in vitro, treated by 10muM melatonin, and injected into the heart of a mouse with myocardial infarction, and the heart function of the mouse is detected by a B-typeultrasonic Doppler instrument; found by results, the melatonin can effectively resist the oxidative stress loss of the CPCs, increase the cell proliferation ability of the injured CPCs, and inhibit the withering, and meanwhile, the melatonin has the function of promoting the cardiac stem cell transplanting for treating the myocardial infarction. The application has the advantages that the treatment effect of a patient with myocardial infarction is certainly improved, the disease and death rate is reduced, and a new technical means is provided for the treatment of the myocardial infarction.

Description

technical field [0001] The invention relates to a new therapeutic application of melatonin, in particular to the application of melatonin in promoting myocardial stem cell transplantation for treating myocardial infarction. The invention belongs to the technical field of medicine. Background technique [0002] Myocardial infarction is caused by coronary artery thrombus or branch blockage formed by coronary atherosclerosis, which causes severe and persistent acute ischemia of the corresponding myocardium, eventually leading to ischemic necrosis of the myocardium, which may be complicated by arrhythmia, heart failure or shock. life threatening. Cardiomyocytes in adults lack the ability to regenerate and repair. Once necrotic, cardiomyocytes in the infarcted area will form scar tissue, making it difficult to recover heart function and eventually lead to death. At present, the treatment methods for myocardial infarction mainly include drug therapy, surgical treatment and inter...

Claims

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Application Information

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IPC IPC(8): A61K31/4045A61P9/10
CPCA61K31/4045
Inventor 蔡本志袁野杜伟杰马文亚
Owner HARBIN MEDICAL UNIVERSITY
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