Application of Neogenin to preparation of medicine for preventing, relieving and/or treating myocardial infarction and related diseases thereof

A technology for myocardial infarction and ischemic cardiomyopathy, applied to the multifunctional transmembrane receptor neogenin, the application of medicines for relieving and/or treating myocardial infarction and its related diseases, and the preparation of preventive fields, which can solve problems such as unclear effects

Inactive Publication Date: 2021-08-06
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the role of Neo1 in myocardial infarction remains unclear

Method used

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  • Application of Neogenin to preparation of medicine for preventing, relieving and/or treating myocardial infarction and related diseases thereof
  • Application of Neogenin to preparation of medicine for preventing, relieving and/or treating myocardial infarction and related diseases thereof
  • Application of Neogenin to preparation of medicine for preventing, relieving and/or treating myocardial infarction and related diseases thereof

Examples

Experimental program
Comparison scheme
Effect test

experiment example 1

[0026] Experimental example 1Neo1 neutralizing antibody aggravates cardiac function after myocardial infarction

[0027] 1. Inject Neo1 neutralizing antibody

[0028] Neo1 neutralizing antibody (product number AF1079) was purchased from RD Company in the United States, which can effectively bind to the receptor Neo1, block the interaction between Neo1 and its related ligands, and complete the function inhibition of Neo1 in vivo. Two hours before myocardial infarction, the mice were fixed, and Neo1 neutralizing antibody (the solvent was saline) was injected through the tail vein at a dose of 2 μg / mouse, and the control group was given a placebo (vehicle, saline). The experiment was divided into 4 groups according to the random and blind principle: no operation (sham)+vehicle, sham+Anti-Neo1, myocardial infarction group (MI)+vehicle, MI+Anti-Neo1.

[0029] 2. Myocardial infarction model acquisition

[0030] (1) Anesthetized by intraperitoneal injection of 3% pentobarbital sodi...

experiment example 2

[0040] Experimental example 2Neo1 neutralizing antibody increases infarct size and aggravates myocardial remodeling after myocardial infarction

[0041] 1. 2,3,5-Triphenyltetrazolium chloride (2,3,5-Triphenyltetrazolium chloridej, TTC) staining

[0042] (1) After the mice were sacrificed 3 days after myocardial infarction, the heart tissue was quickly taken out and placed in 10% KCl solution.

[0043] (2) After washing the heart, place it in a -20°C refrigerator for 30 minutes.

[0044] (3) The heart tissue was taken out and sliced ​​uniformly along the long axis of the heart from the apex to the bottom of the heart. The slices were immediately placed in 10 mL of 2% TTC solution and incubated at a constant temperature of 37°C for 20 min. Normal heart tissue stained bright red, while the infarct area was pale.

[0045] (4) The brain tissue slices were fixed with 10% neutral formalin solution, the gross photographs were taken, and the infarct area was calculated.

[0046] 2. ...

experiment example 3

[0108] Experimental example 3Neo1 neutralizing antibody aggravates cardiomyocyte apoptosis after myocardial infarction

[0109] 3.1 Western Blot monitoring of apoptosis-related proteins

[0110] Protein extraction, electrophoresis gel as above, using the primary antibodies Bax, Bcl-2 and GAPDH.

[0111] 3.2 Immunofluorescence

[0112] 3.2.1 Preparation of paraffin specimens and sections

[0113] (1) The mouse heart tissue was taken out from the 10% formalin solution, the heart tissue was trimmed in a fume hood, and the trimmed heart tissue and the corresponding label were placed in a dehydration box.

[0114] (2) Dehydration and wax dipping: Put the dehydration box into the dehydrator for dehydration and wax dipping treatment. 75% ethanol (4h)→85% ethanol (2h)→90% ethanol (2h)→95% ethanol (1h)→absolute ethanol I (30min)→absolute ethanol II (30min)→alcohol benzene (5-10min )→xylene I (5-10min)→xylene II (5-10min)→65°C melted paraffin I (1h)→65°C melted paraffin II (1h)→65°C...

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Abstract

The invention discloses an application of Neogenin to preparation of a medicine for preventing, relieving and / or treating myocardial infarction and related diseases thereof, and belongs to the field of functions and application of genes. According to the invention, the research results show that a Neogenin (Neo1) neutralizing antibody can aggravate myocardial remodeling after myocardial infarction, and can deteriorate cardiac functions. Research results show that Neo1 shows a protective effect in myocardial infarction, the Neo1 is taken as a target or the Neo1 can be used for preparing the medicine for preventing, relieving and / or treating myocardial infarction and related diseases thereof, and myocardial infarction and related diseases thereof comprise acute ST segment elevation type myocardial infarction, acute non-ST segment elevation type myocardial infarction, ischemic cardiomyopathy, heart failure and the like. According to the pharmaceutical application, the Neo1 is used as a medicine, a Neo1 activator is used as a medicine, and a substance for promoting Neo1 expression is used as a medicine. The invention provides a new medicine for preventing, relieving and / or treating myocardial infarction.

Description

technical field [0001] The invention belongs to the field of gene function and application, and relates to a multifunctional transmembrane receptor neogenin (Neo1) of the immunoglobulin superfamily. Specifically, Neo1 is used as an intervention target in the preparation of prevention, alleviation and / or treatment The application of drugs in myocardial infarction and its related diseases. Background technique [0002] Myocardial infarction (abbreviated as MI) refers to the persistent ischemia and hypoxia of myocardial cells caused by a sharp reduction or interruption of coronary blood flow, which eventually leads to irreversible necrosis of myocardial cells. According to the data of "China Cardiovascular Health and Disease Report 2019", the mortality rate of acute myocardial infarction in my country was on the rise from 2002 to 2017. population), resulting in a heavy health burden [1]. At present, the significant increase in the treatment rate of emergency PCI in my country ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61K45/00A61P9/10
CPCA61K38/1774A61K45/00A61P9/10
Inventor 万军王梦龙张记收徐瑶赵蒙蒙刘剑芳于君平徐姝婉潘威叶晶王震叶迪冯勇淇
Owner WUHAN UNIV
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