Application of alpha-ketoglutaric acid in preparation of medicine for treating myocardial infarction

A technique for myocardial infarction and ketoglutaric acid, which is applied in the field of biomedicine and can solve the problems of α-ketoglutaric acid affecting myocardial cell proliferation and the like

Pending Publication Date: 2022-02-11
中国人民解放军陆军特色医学中心
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, whether α-ketoglutarate can affect the proliferation of cardiomy

Method used

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  • Application of alpha-ketoglutaric acid in preparation of medicine for treating myocardial infarction
  • Application of alpha-ketoglutaric acid in preparation of medicine for treating myocardial infarction
  • Application of alpha-ketoglutaric acid in preparation of medicine for treating myocardial infarction

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] α-ketoglutarate can promote the proliferation of primary cardiomyocytes cultured in vitro

[0035] The cardiomyocytes of neonatal SD rats were extracted, and the specific method was as follows:

[0036] (1) Prepare 10 ml of type II collagenase and trypsin solutions with concentrations of 0.08% and 0.125%, respectively.

[0037] (2) The ventricle tissue of suckling mice was cut out by ophthalmologist, and stored in pre-cooled Hanks buffer.

[0038] (3) Shred the tissue to 1mm 3 Small pieces, then rinse again with pre-cooled Hanks buffer solution.

[0039] (4) Suck off the washing solution, add an appropriate amount of trypsin, gently pipette repeatedly for 1 minute, and discard the liquid after the tissues have gathered into a ball.

[0040] (5) Add collagenase, blow off, and digest at 37°C for 30 minutes.

[0041] (6) Gently tap and beat repeatedly, and after the tissue block dissolves, add 1 ml of fetal bovine serum to terminate digestion.

[0042] (7) Filter the ...

Embodiment 2

[0049] α-ketoglutarate can promote the proliferation of cardiomyocytes in developing mice

[0050] The 7-day-old mice were divided into the experimental group and the control group, and received intraperitoneal injection of α-ketoglutarate and PBS every day, and the heart weight ratio was evaluated after 2 weeks, and further detected by wheat germ agglutinin (WGA) staining Cardiomyocyte size. The results showed that injection of α-ketoglutaric acid could increase the heart weight ratio of mice ( Figure 4 ), but the volume of cardiomyocytes did not change significantly ( Figure 5 ). The expression of proliferation markers (EdU pulse labeling) was detected by immunofluorescent staining, such as Figure 6 As shown, α-ketoglutarate injection can promote the proliferation of cardiomyocytes in mice.

Embodiment 3

[0052] α-Ketoglutarate improves post-infarction cardiac function and infarct size and promotes proliferation of adult cardiomyocytes

[0053] (1) To construct a mouse model of myocardial infarction, divide the mice into the experimental group and the control group, and receive daily intraperitoneal injection of α-ketoglutarate and PBS after myocardial infarction. After continuous injection for 2 weeks, two-dimensional echocardiography Cardiac function detected by graph (EF%, FS%, LVIDs and LVIDd at 4th week after operation); Masson staining was used to detect myocardial infarct size (4th week after operation); expression of proliferation markers was detected by immunofluorescent staining (EdU pulse marker ). The results showed that α-ketoglutarate could improve cardiac function ( Figure 7 ), reducing the infarct size ( Figure 8 ), promote the proliferation of adult cardiomyocytes ( Figure 9 ).

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Abstract

The invention discloses application of alpha-ketoglutaric acid in preparation of a medicine for treating myocardial infarction. A metabolic intermediate alpha-ketoglutaric acid used in the invention can improve heart function decline caused by myocardial infarction and reduce the myocardial infarction area by promoting proliferation of adult myocardial cells. The specific mechanism is as follows: the alpha-ketoglutaric acid activates the activity of demethylase JMJD3 and enhances the demethylation effect of the alpha-ketoglutaric acid on H3K27me3, so that the inhibition of transcriptional histone modified H3K27me3 on a cell cycle adjusting gene is relieved, the proliferation of adult myocardial cells is finally promoted, and the purposes of repairing myocardial infarction and preventing and treating heart failure are achieved. The alpha-ketoglutaric acid provided by the invention can be used for treating myocardial infarction, and has important clinical significance for treating myocardial infarction.

Description

technical field [0001] The invention belongs to the field of biomedical research, and in particular relates to the application of alpha-ketoglutarate in the preparation of medicine for treating myocardial infarction. Background technique [0002] Myocardial infarction is one of the major diseases that endanger human health, with the characteristics of high incidence and poor prognosis. After myocardial infarction, a large number of myocardial cells undergo necrosis and apoptosis. Because the adult myocardium cannot repair itself through self-proliferation, the heart function continues to deteriorate, and eventually develops into heart failure. Drug therapy, interventional therapy, coronary artery bypass grafting and other methods currently used clinically can help improve the symptoms of patients and restore blood supply, but none of them can fundamentally renew and repair necrotic myocardium. Therefore, the restoration of cardiac function ultimately depends on myocardial r...

Claims

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Application Information

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IPC IPC(8): A61K31/194A61P9/10
CPCA61K31/194A61P9/10
Inventor 曾春雨王伟时宇夏雪伟
Owner 中国人民解放军陆军特色医学中心
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