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Application of miRNA in the treatment of cardiac hypertrophy

A technique for myocardial hypertrophy and cardiac load, applied in the field of medicine and biology, can solve the problems of poor clinical effect of drugs

Active Publication Date: 2021-04-27
BEIJING INST OF HEART LUNG & BLOOD VESSEL DISEASES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Although a large number of studies have shown that multiple signaling molecules are involved in cardiac hypertrophy, in addition to drugs such as ARB, multiple targets discovered based on animal experiments have not been successfully translated into clinical practice, which may be due to the huge differences between humans and animals. poor clinical effect

Method used

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  • Application of miRNA in the treatment of cardiac hypertrophy
  • Application of miRNA in the treatment of cardiac hypertrophy
  • Application of miRNA in the treatment of cardiac hypertrophy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1. Supplementation of hsa-miR-15a-5p / hsa-miR-16-5p (delivered by CHO-PEGA cation carrier) in vitro inhibits cardiac hypertrophy

[0037] The therapeutic effect of hsa-miR-15a-5p / hsa-miR-16-5p supplementation was tested.

[0038] Culture embryonic rat cardiomyocyte cell line (H9C2 cell line) in DMEM supplemented with 10% heat-inactivated fetal calf serum and antibiotics, culture embryonic rat cardiomyocyte cell line (H9C2 cell line) in a 24-well plate, and then add 20 μL CHO-PGEA-miRNA complex.

[0039] The preparation of the CHO-PGEA-miRNA complex can refer to the previous work of the applicant (such as CN201510377896.X, CN201910327563.4): mix the ingredients in the following table 3, shake for 5 seconds and then let stand for 30 minutes:

[0040] Table 3. Components of CHO-PGEA-miRNA complexes

[0041]

[0042] Cells were divided into negative control group and experimental group.

[0043] (1) Negative control group: 20 μL LCHO-PEGA-mirNC (no functional m...

Embodiment 2

[0058] Example 2. In vivo supplementation of hsa-miR-15a-5p / hsa-miR-16-5p (delivered by CHO-PEGA cation carrier) can completely inhibit TAC-induced cardiac hypertrophy and improve myocardial fatty acid oxidation

[0059] 1. Modeling steps of mouse TAC model:

[0060] (1) The mice were fixed under induction anesthesia. Maintain anesthesia with 1.5% isoflurane mixed gas through tracheal intubation;

[0061] (2) Disinfect the surgical area and prepare the skin for thoracotomy. Exposure of the thoracic aorta after thoracotomy;

[0062] (3) At the aortic arch, a 27G thin needle was placed parallel to the aortic arch and ligated together;

[0063] (4) After the ligation, draw out the fine needle to observe the condition of the mouse, and suture layer by layer after the condition is stable.

[0064] 2. Experimental grouping and scheme ( figure 2 A)

[0065] Select 15 wild mice and divide them into 3 groups, including:

[0066] (1) 5 mice in the blank control group: inject nor...

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Abstract

The present invention relates to the application of miRNA in the treatment of myocardial hypertrophy. Specifically, the miRNA is hsa-miR-15a-5p / hsa-miR-16-5p, and its nucleotide sequences are respectively as SEQ ID NO.1 and SEQ ID NO.1. Shown in ID NO.2. The cardiac hypertrophy refers to a pathophysiological process mainly characterized by thickening of the ventricular muscle and narrowing of the chamber caused by the overload of the heart caused by heredity, hypertension, myocardial infarction, valvular disease and the like. The present invention also relates to the application of the complex loaded with hsa-miR-15a-5p / hsa-miR-16-5p in the preparation of medicine for treating myocardial hypertrophy, the complex being CHO-PGEA-nucleic acid complex.

Description

technical field [0001] The invention belongs to the field of medical biotechnology, and specifically relates to the application of miRNA in the treatment of cardiac hypertrophy. Background technique [0002] Cardiovascular disease is still the leading cause of death, and its morbidity and mortality are increasing year by year. The heart responds to injury caused by myocardial infarction or sustained pressure overload through a variety of structural changes, commonly referred to as cardiac remodeling. At the cellular level, these changes include changes in cardiac hypertrophy, cardiomyocyte apoptosis, and expression of genes that regulate energy metabolism. Among them, myocardial hypertrophy is the main pathological process of hypertensive heart disease, hypertrophic cardiomyopathy and other cardiovascular diseases. Persistent myocardial hypertrophy can lead to heart failure and sudden death, which is an independent risk factor for cardiovascular disease. In general, myoca...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/7088A61P9/04
CPCA61K31/7088A61P9/04
Inventor 杜杰李玉琳许晨郝文静
Owner BEIJING INST OF HEART LUNG & BLOOD VESSEL DISEASES
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