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Medical application of CREG protein to myocardial Ischemia-reperfusion injury protection

A technology for reperfusion injury and myocardial ischemia, which is applied in the medical field of CREG protein to protect myocardial ischemia-reperfusion injury, and can solve unclear problems

Active Publication Date: 2015-12-30
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

In recent years, it has been discovered that CREG is a lysosomal protein, but its specific effect on cells and its mechanism, as well as its relationship with myocardial ischemia-reperfusion injury, are still unclear

Method used

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  • Medical application of CREG protein to myocardial Ischemia-reperfusion injury protection
  • Medical application of CREG protein to myocardial Ischemia-reperfusion injury protection
  • Medical application of CREG protein to myocardial Ischemia-reperfusion injury protection

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Example 1. Giving mice myocardial ischemia-reperfusion treatment can down-regulate the expression of CREG protein in the myocardium

[0053] ①Establishment of myocardial ischemia-reperfusion model in mice

[0054] Prepare various instruments, materials and medicines before the operation; the steps and methods of thoracotomy and ligation of the left anterior descending coronary artery: cut the skin 2 mm to the left side of the sternum, bluntly separate the muscles to see the ribs, and gently use ophthalmic scissors in the fourth intercostal space The intercostal muscles were separated downward, and the vascular forceps were extended upward to repeatedly clamp the two ribs to reduce bleeding. Cut ribs 3 and 4, pull apart the chest wall with retractors, thread a pair of threads on the chest wall muscles on both sides and leave small loops on the inside. Carefully cut the pericardium and apply gentle pressure to the heart with a cotton swab. Insert the needle at about 2 m...

Embodiment 2

[0073] Example 2. Changes in the expression of CREG protein in mouse myocardium can affect the heart function of mice

[0074] ① CREG at 28 days after myocardial ischemia-reperfusion + / + and CREG + / - Comparison of heart function. The Vevo2100 ultrasonic biomicroscope imaging system from VisualSonics Corporation of Canada was adopted, and the center frequency of the probe was 30MHz. After the mice were anesthetized with 2% isoflurane, the hair on the chest and abdomen was removed. The mice were fixed in a supine position on a constant temperature inspection table, and the temperature was kept at 37°C. The physiological parameters such as ECG and respiration were recorded synchronously. The heart rate was maintained at about 450 beats / min. After the heart rate was stable for 1 min, smear coupling agent on the chest and perform ultrasound biomicroscopy. examine. The results showed that after 28 days of myocardial ischemia-reperfusion, CREG + / - CREG + / + The cardiac function ...

Embodiment 3

[0078] Example 3. Administration of exogenous recombinant CREG protein during myocardial ischemia-reperfusion can reduce the apoptosis of mouse cardiomyocytes and further activate the occurrence of autophagy

[0079] ①The apoptosis of cardiomyocytes in the myocardium of three kinds of mice was detected by Tunel staining. After preparing the necessary reagents for Tunel staining, the frozen tissue sections were fixed in 4% paraformaldehyde at room temperature for 10 min, and washed twice with PBS, 10 min each time. After 20 minutes with 3% hydrogen peroxide methanol solution, wash with PBS 3 times, 5 minutes each time, place on ice with 0.1% sodium citrate for 2 minutes, add Tunel staining solution to the surface of the sample, and incubate in a 37°C incubator for 1 hour, protected from light; soak in PBS , DAPI stained nuclei. The results suggest that after myocardial ischemia-reperfusion CREG + / - The mice had the most cardiomyocyte apoptosis, while the mice given exogenous ...

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Abstract

The invention relates to application of CREG protein, in particular to application of the CREG protein or an active fragment of the CREG protein to preparation of drugs for preventing and / or treating myocardial Ischemia-reperfusion injury. The invention further relates to application of a recombinant vector or recombinant cell expressing the CREG protein or an active fragment of the CREG protein to preparation of the drugs for preventing and / or treating the myocardial Ischemia-reperfusion injury. The invention further relates to a preparation compound which contains the CREG protein or an active fragment of the CREG protein as well as the recombinant vector or recombinant cell expressing the CREG protein or the active fragment of the CREG protein, and can inhibit down-regulated expression of the CREG protein or an active fragment of the CREG protein or promote up-regulated expression of the CREG protein or an active fragment of the CREG protein.

Description

technical field [0001] The present invention relates to the medical use of E1A activating gene repressor (CREG) protein, in particular to the use of CREG protein or its active fragments for preparing medicines with definite protective effect on myocardial ischemia-reperfusion injury. Background technique [0002] Myocardial ischemia-reperfusion (MIR) injury refers to the restoration of blood perfusion of myocardial tissue after a long period of ischemia, but more obvious and more serious damage and dysfunction than before reperfusion, including decreased systolic function, coronary blood Decreased flow and changes in vascular reactivity. At present, for acute coronary infarction, medical drugs, interventional therapy, and coronary artery bypass grafting are mainly used to recanalize coronary arteries, and myocardial reperfusion injury may also occur. Studies have shown that the mechanism of MIR injury mainly includes oxygen free radicals, infiltration of neutrophils, produc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61K48/00A61K45/00A61P9/10G01N33/68
Inventor 韩雅玲闫承慧宋海旭田孝祥李洋
Owner GENERAL HOSPITAL OF THE NORTHERN WAR ZONE OF THE CHINESE PEOPLES LIBERATION ARMY
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