Medical application of CREG protein in preventing or treating myocardial infarction

A technology for acute myocardial infarction and myocardial infarction, which is used in the preparation of drugs for the prevention or treatment of myocardial infarction, the field of CREG protein or its active fragment, and can solve problems such as unclear action and mechanism

Active Publication Date: 2015-11-18
GENERAL HOSPITAL OF THE NORTHERN WAR ZONE OF THE CHINESE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the effect and mechanism of CREG protein on cardiomyocyte injury and heart failure after AMI are still unclear

Method used

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  • Medical application of CREG protein in preventing or treating myocardial infarction
  • Medical application of CREG protein in preventing or treating myocardial infarction
  • Medical application of CREG protein in preventing or treating myocardial infarction

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0081] Example 1. Preparation of AMI model in C57BL / 6J mice and detection of CREG expression in myocardial tissue at different time points after AMI.

[0082] ①Establishment of AMI model in C57BL / 6J mice

[0083]The mouse model of AMI was established by ligation of the anterior descending coronary artery. Various instruments, materials and medicines were prepared before the operation; mice were anesthetized with 3% chloral hydrate (450mg / kg) intraperitoneally and fixed on the mouse board in supine position. Endotracheal intubation, connected to a ventilator. The preoperative standard II lead ECG was measured and stored in the computer. Cut off the hair in the chest operation area, cut the skin, subcutaneous tissue, chest muscle and fascia 3-4 cm, open the chest cavity, and use a (6-0) suture needle to ligate the middle and upper 1 / 3 of the left anterior descending coronary artery parts. The successful ligation was marked by the high and wide QRS wave (the S-T segment of th...

Embodiment 2

[0101] Embodiment 2: establish the CREG heterozygote (CREG of CREG low expression) + / - ) mouse model, CREG + / - CREG expression decreased in mouse myocardial tissue.

[0102] ①CREG + / - Mice preparation and genotype identification: CREG was established through China Shanghai Southern Model Animal Center + / - knockout mice. Specific method: After deleting 2-3 exons of the mouse CREG1 gene (EnsemblGeneID: ENSMUSG000000111432), the CREG gene is mutated, leading to premature termination of protein translation. Insert the Neo element between introns 1-2 and introns 3-4 (see figure 2 A). The targeting vector used was the CREG1-ABRFn-pBR322 plasmid (see figure 2 B). The PCR-Genotyping method was used for genotyping and identification according to the following reaction system and reaction conditions.

[0103] 1) 5'armPCR identification: P1Creg1-5P112-ATGTGCACAGTCATGGTTTCTCC (SEQ ID NO: 1), P2neoreverse-GGCCTACCCGCTTCCATTGCTC (SEQ ID NO: 2); the amplification position is plasmi...

Embodiment 3

[0137] Example 3: Compared to littermate control mice, CREG + / - Mortality was significantly increased in mice after AMI; systolic function was significantly worsened and ventricular remodeling was aggravated.

[0138] ①CREG + / - The establishment of the AMI model of mice and littermate control mice was the same as in Example 1.

[0139] ②CREG + / - Survival analysis of mice and littermate control mice after AMI.

[0140] After AMI in mice, the number of dead mice was observed and recorded every day, and the survival curve was drawn.

[0141] The results showed that compared with littermate control mice, CREG + / - The 28-day mortality rate of mice after AMI was significantly increased (results in image 3 A).

[0142] ③Evaluation of cardiac systolic function in mice by ultrasound of small animals:

[0143] The mice were anesthetized with isoflurane, and the systolic function was detected with Vevo2100 small animal echocardiography. The physiological parameters such as elect...

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Abstract

The invention relates to application of E1A-simulated gene cellular repressor (CREG) protein, in particular to application of CREG protein or active fragment thereof in preparation of drug used for preventing and/or treating acute myocardial infarction, heart failure after acute myocardial infarction and/or ventricular remodeling after the same. The invention further relates to application of recombinant vector or recombinant cell expressing the CREG protein or the active fragment thereof in preparation of the drug used for preventing and/or treating acute myocardial infarction, heart failure after acute myocardial infarction and/or ventricular remodeling after the same.

Description

technical field [0001] The present invention relates to the medical use of E1A activated gene repressor (Cellular Repressor of E1A-stimulated Genes, CREG), in particular to the use of CREG protein or its active fragments for the preparation of drugs for preventing or treating myocardial infarction. The present invention also relates to the use of the CREG protein or its active fragments for the preparation of drugs for preventing and / or treating ventricular remodeling after myocardial infarction and heart failure after myocardial infarction. Background technique [0002] Coronary Heart Disease (CHD) is one of the major diseases that seriously threaten human health and life. Its main manifestations—acute myocardial infarction (AMI) and post-infarction heart failure are important causes of death in CHD patients. According to the "China Cardiovascular Disease Research Report" released in 2013, there are at least 500,000 new cases of AMI in China every year, and about 2.5 millio...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/14A61K48/00A61K45/00A61P9/10A61P9/04C12Q1/68
Inventor 韩雅玲刘丹田孝祥闫承慧张效林
Owner GENERAL HOSPITAL OF THE NORTHERN WAR ZONE OF THE CHINESE PEOPLES LIBERATION ARMY
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