Use of lysophosphatidic acid, lysophosphatidic acid receptor 3, and lysophosphatidic acid receptor 3 agonists

A technology of lysophosphatidic acid and receptors, applied in the field of biomedicine

Active Publication Date: 2020-05-22
FUWAI HOSPITAL CHINESE ACAD OF MEDICAL SCI & PEKING UNION MEDICAL COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, the drugs and methods for treating heart disease, especially ischemic heart disease, are still relatively limited, and more drugs and methods for treating heart disease need to be developed

Method used

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  • Use of lysophosphatidic acid, lysophosphatidic acid receptor 3, and lysophosphatidic acid receptor 3 agonists
  • Use of lysophosphatidic acid, lysophosphatidic acid receptor 3, and lysophosphatidic acid receptor 3 agonists
  • Use of lysophosphatidic acid, lysophosphatidic acid receptor 3, and lysophosphatidic acid receptor 3 agonists

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Effects of LPA3 overexpression on cardiac function and infarct size after myocardial infarction in mice

[0041] (1) Establishment of mouse myocardial infarction model

[0042]After weighing and recording the body weight of the mice, they were anesthetized by intraperitoneal injection of tribromoethanol solution at a concentration of 400 mg / kg (about 0.2 mL for mice with about 25 ng);

[0043] Disinfect the left chest of the mouse with 75% alcohol, use depilatory cream to remove the hair near the surgical field of view; carry out tracheal intubation, and connect the ventilator;

[0044] Cut the skin on the outside of the left chest along the parallel direction of the left ribs, bluntly separate the muscles of each layer along the direction of the muscle shape to expose the ribs, and use a spreader to stretch the muscles so that the rib layer is exposed in the center of the field of vision; in the 3rd-4th intercostal space Use fine straight forceps to separate the muscl...

Embodiment 2

[0057] Effect of overexpression of LPA3 on the proliferation of cardiomyocytes after myocardial infarction in mice

[0058] (1) Experimental grouping and processing

[0059] With embodiment 1.

[0060] (2) Experimental method

[0061] Using a mouse model of myocardial infarction, LPA3 overexpression and control viruses were injected into the infarction area at the same time, and heart samples were collected 8 weeks after myocardial infarction, and the myocardial marker α-s-actin and proliferation marker Ki67 were co-stained by immunofluorescence. pH3. The specific method is to dewax the prepared paraffin slices and carry out antigen retrieval. After washing with phosphate buffer, block with goat serum for 1 hour, and then add an appropriate concentration of primary antibody (anti-α-s-actin, Ki67 or pH3)4 Incubate overnight at ℃, wash with phosphate buffer, add appropriate concentrations of secondary antibodies with different fluorescence and incubate at 37°C in the dark for...

Embodiment 3

[0065] Effect of overexpression of LPA3 on myocardial cell apoptosis after myocardial infarction in mice

[0066] (1) Experimental grouping and processing

[0067] With embodiment 1.

[0068] (2) Experimental method

[0069] Using a mouse model of myocardial infarction, LPA3 overexpression and control viruses were injected into the infarct area at the same time as the infarction, and heart samples were collected 8 weeks after myocardial infarction, and the apoptosis of myocardial cells in the peri-infarction area and infarct distal end was detected by TUNEL experiment. The specific method In order to dewax the prepared paraffin slices, pretreat with proteinase K to break the cell membrane, then block with goat serum for 1 hour, add an appropriate concentration of cTNT antibody and incubate overnight at 4°C, wash with phosphate buffer and add an appropriate concentration of fluorescence The secondary antibody was incubated at 37°C in the dark for 1 hour, washed with phosphate...

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Abstract

The invention discloses application of lysophosphatidic acid, a lysophosphatidic acid receptor 3 and a lysophosphatidic acid receptor 3 agonist and relates to the field of biomedicine. The study findsout that lysophosphatidic acid or the lysophosphatidic acid receptor 3 or the lysophosphatidic acid receptor 3 agonist can promote cardiomyocyte proliferation and inhibit cardiomyocyte apoptosis to repair damaged myocardia, significantly reduce myocardial infarct areas and significantly improve cardiac functions after myocardial infarction, and the effect is obvious. Therefore, lysophosphatidic acid, the lysophosphatidic acid receptor 3 and the lysophosphatidic acid receptor 3 agonist can be used in the field of preparation of medicine, preparations and the like for treating or preventing heart diseases, and new medicine and a new treatment idea are provided for treating or preventing heart diseases such as ischemic heart disease.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the application of lysophosphatidic acid, lysophosphatidic acid receptor 3 and lysophosphatidic acid receptor 3 agonist. Background technique [0002] Heart disease is the leading cause of death in adults worldwide. Ischemic coronary artery disease and high blood pressure can all lead to heart disease, resulting in decreased heart function, arrhythmia, heart failure and death. The adult mammalian heart cannot effectively Generate new cardiomyocytes to replace damaged myocardium. Although many drugs and mechanical devices can improve cardiac function, these methods cannot replace lost cardiomyocytes, so new strategies are needed to treat myocardial injury. Promoting myocardial regeneration and inhibiting cardiomyocyte apoptosis are important strategies for repairing damaged myocardium. [0003] Stem cell transplantation is an important direction of myocardial regeneration therapy, but ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/661A61K38/17A61P9/10A61P9/04A61P9/00
CPCA61K31/661A61K38/177A61P9/00A61P9/04A61P9/10
Inventor 陈曦胡盛寿王芳刘思蔡琳丛祥凤
Owner FUWAI HOSPITAL CHINESE ACAD OF MEDICAL SCI & PEKING UNION MEDICAL COLLEGE
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