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Function and application of dickkopf-3 (dkk3) gene in coronary atherosclerotic heart disease

A technology for coronary atherosclerosis and heart disease, applied in gene therapy, cardiovascular system diseases, pharmaceutical formulations, etc., can solve problems such as inability to effectively and completely repair myocardial tissue, death, arrhythmia, etc.

Active Publication Date: 2016-03-30
武汉惠康达科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

After myocardial infarction, only a small number of myocardial cells divide and proliferate, unable to effectively and completely repair myocardial tissue. Therefore, the myocardium in the infarcted area can only be replaced by scar tissue without contractile function through fibrous tissue hyperplasia, thereby causing severe arrhythmia, Heart failure or even death

Method used

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  • Function and application of dickkopf-3 (dkk3) gene in coronary atherosclerotic heart disease
  • Function and application of dickkopf-3 (dkk3) gene in coronary atherosclerotic heart disease
  • Function and application of dickkopf-3 (dkk3) gene in coronary atherosclerotic heart disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] [Example 1] Myocardial infarction (MI) model acquisition

[0029] 1. Grouping of experimental animals: male C57BL / 6 background mice (DKK3+ / +), DKK3 knockout mice (DKK3- / -), heart-specific DKK3 transgenic mice (DKK3-TG) and non-transgenic mice ( NTG), a myocardial infarction (MI) model was induced by ligation of the left anterior descending coronary artery (LAD) of the mouse heart. They were randomly divided into 8 groups, each group: C57BL / 6 background a-MHC-Cre mouse sham operation group (DKK3+ / +Sham) and MI operation group (DKK3+ / +MI), DKK3 gene knockout mouse sham operation group ( DKK3- / -Sham) and MI operation group (DKK3- / -MI), non-transgenic mouse sham operation group (NTGSham) and MI operation group (NTGMI), heart-specific DKK3 transgenic mouse sham operation group (DKK3-TGSham ) and MI group (DKK3-TGMI).

[0030] 2. The MI model uses blocking the left anterior descending coronary artery (LAD) of the mouse heart to cause myocardial infarction. The operation pro...

Embodiment 2

[0039] [Example 2] Detection of myocardial infarction ratio, myocardial hypertrophy and fibrosis in mouse myocardial infarction (MI) model

[0040] 1. Take materials

[0041] (1) Preliminary work: prepare a urine cup filled with 20mL of 10% formaldehyde in advance, and label it (mouse number, group, type of operation and date of collection). Place the petri dish filled with 10% KCl solution at the sampling site. Turn on the analytical balance, adjust to zero, and then weigh and kill the mice.

[0042] (2) Material collection: Ophthalmic curved forceps clamped the vascular pedicle below the atrial appendage, cut off the heart, and quickly placed it in 10% KCl solution. After the heart stops beating in the diastolic phase, place it on sterilized gauze, gently squeeze the fluid in the heart cavity, dip the surface fluid dry, weigh and record, put the heart into the corresponding urine cup, fix it for 48 hours and use it for pathological testing.

[0043] (3) Relevant measurem...

Embodiment 3

[0063] [Example 3] Detection of cardiac function in myocardial infarction (MI) model mice

[0064]1 Ultrasound detection of cardiac function

[0065] 1.1 Preliminary preparation

[0066] (1) Anesthesia machine preparation: first connect the oxygen cylinder and the air inlet port on the anesthesia machine, then unscrew the sealing cap of the dosing port on the anesthesia machine, quickly add isoflurane to the safety scale, and then tighten the sealing cap. Unscrew the main valve on the oxygen cylinder, adjust the knob of the flow control valve, and maintain the outlet pressure at 0.2-0.3mPa.

[0067] (2) Preparation of the mice to be tested: After the mice to be tested were quickly anesthetized with isoflurane, the hair on the left chest area was shaved, and the head of the treated mice was inserted into the anesthetic catheter sleeve, and treated with 1.5-2.0% isoflurane Alkane maintains a stable anesthesia in mice.

[0068] 1.2 Cardiac function test

[0069] The mice were...

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Abstract

The invention discloses the function and application of a DKK3 gene in coronary atherosclerotic heart disease. The present invention takes DKK3 gene knockout mice and heart-specific DKK3 transgenic mice as experimental objects, and studies the myocardial infarction model by blocking the left anterior descending coronary artery of the mouse heart. The results show that compared with DKK3+ / + control mice , the proportion of myocardial infarction, myocardial hypertrophy and fibrosis in DKK3 knockout mice was significantly increased, and the cardiac function was significantly deteriorated; while the proportion of cardiac infarction, myocardial hypertrophy and fibrosis in cardiac-specific DKK3 transgenic mice was significantly suppressed, Cardiac function improved significantly. Therefore, it was discovered that the function of the DKK3 gene in coronary atherosclerotic heart disease is mainly reflected in its ability to protect coronary atherosclerotic heart disease. Aiming at the above functions of DKK3, DKK3 can be used to prepare medicines for treating coronary atherosclerotic heart disease.

Description

technical field [0001] The invention belongs to the field of gene function and application, in particular to the function and application of a Dickkopf-3 (DKK3) gene in coronary atherosclerotic heart disease. Background technique [0002] Cardiovascular disease is the disease that causes the highest death rate in the world and is the number one killer of human health. Ischemic heart disease is the main cause of death from cardiovascular diseases. Myocardial infarction (MI) is a common type of ischemic heart disease. If the blood supply of the myocardium is blocked for more than 30 minutes, the ultrastructural changes of various organelles will be caused. The changes and dysfunction of cardiomyocytes lead to irreversible damage and even death of cardiomyocytes. Acute myocardial infarction is a critical disease of cardiovascular disease. Within a few minutes after the onset of acute myocardial infarction, the myocardial cells in the ischemic central area will die due to ische...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K48/00A61P9/10
Inventor 李红良蒋丁胜王丕晓刘小熊
Owner 武汉惠康达科技有限公司
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