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Application of bone morphogenic protein-4 in screening anti-cardiac hypertrophy, anti-heart failure or anti-cardiac fibrosis drugs

A technology for cardiac fibrosis and cardiac hypertrophy, applied in the field of application of bone morphogenic protein-4 in the screening of anti-cardiac hypertrophy, anti-heart failure or anti-cardiac fibrosis drugs, can solve the problem of inability to completely cure arrhythmia, inability to inhibit cardiac decay process etc.

Active Publication Date: 2014-10-01
HARBIN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These drugs mainly improve the symptoms of heart failure but cannot inhibit the progress of heart failure, and improve the symptoms of arrhythmia but cannot completely cure arrhythmia. Therefore, it is necessary to develop new drugs that can inhibit the development of myocardial hypertrophy, heart failure, and arrhythmia.

Method used

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  • Application of bone morphogenic protein-4 in screening anti-cardiac hypertrophy, anti-heart failure or anti-cardiac fibrosis drugs
  • Application of bone morphogenic protein-4 in screening anti-cardiac hypertrophy, anti-heart failure or anti-cardiac fibrosis drugs
  • Application of bone morphogenic protein-4 in screening anti-cardiac hypertrophy, anti-heart failure or anti-cardiac fibrosis drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] The relationship between embodiment 1 BMP4 and myocardial hypertrophy, heart failure and cardiac fibrosis

[0044] 1. Establishment of pressure load-induced cardiac hypertrophy model

[0045] Mice were anesthetized by intraperitoneal injection of pentobarbital sodium 65 mg / kg, placed supine on a mouse board, and under sterile conditions, tracheal intubation was performed and a ventilator was connected. A median chest incision (1-2 cm) was made to expose and separate the aortic arch. A 26-gauge needle was placed close to the thoracic aorta in parallel, the two were ligated with a 7.0-gauge thread, and the needle was withdrawn after ligation. The chest incision was sutured layer by layer and the chest was closed. Postoperative penicillin sodium intramuscular injection 3d anti-infection. Four weeks later, the mice were anesthetized with sodium pentobarbital, and the mice were sacrificed after weighing their body weight (BW). Heart weight (HW) and left ventricle weight ...

Embodiment 2

[0058] Example 2 The effect of Noggin protein on anti-cardiac hypertrophy, anti-cardiac apoptosis, and anti-cardiac fibrosis

[0059] like figure 2 As shown in e, angiotensin II was used to induce cardiomyocyte hypertrophy in vitro, and administration of Noggin protein could significantly inhibit angiotensin II-induced cardiomyocyte hypertrophy. like figure 2 As shown in d, in cultured cardiomyocytes, BMP4 induced the increase of Caspase-3 activity, and the administration of Noggin protein could significantly inhibit the increase of BMP4-induced cardiomyocyte Caspase-3 activity, indicating that Noggin protein can inhibit cardiomyocyte apoptosis. like image 3 As shown in h, i, in the cultured cardiac fibroblasts, angiotensin II was used to induce fibroblast transformation, and the administration of Noggin protein could significantly inhibit the fibroblast transformation induced by angiotensin II, indicating that Noggin protein has anti-cardiac fibroblast transformation ch...

Embodiment 34

[0061] Example 34-[6-(4-isopropoxy)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline (DD, the structure is shown in formula I) in anti-cardiac hypertrophy, anti-cardiac Apoptosis, anti-cardiac fibrosis

[0062] like figure 2 As shown in e, using angiotensin II to induce hypertrophy of cardiomyocytes in vitro, giving 4-[6-(4-isopropoxy)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline can Significantly inhibits angiotensin II-induced cardiomyocyte hypertrophy. like figure 2 As shown in d, in cultured cardiomyocytes, BMP4 induces an increase in Caspase-3 activity, giving 4-[6-(4-isopropoxy)pyrazolo[1,5-a]pyrimidin-3-yl] Quinoline can significantly inhibit the increase of cardiomyocyte Caspase-3 activity induced by BMP4, indicating that the compound can inhibit cardiomyocyte apoptosis. like image 3 As shown in h, i, in cultured cardiac fibroblasts, angiotensin II was used to induce fibroblast transformation, and administration of this compound could significantly inhibit angiotensin II-induc...

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Abstract

The invention discloses an application of bone morphogenetic protein-4 in screening drugs for resisting cardiac hypertrophy, heart failure or cardiac fibrosis and belongs to the field of biomedicine. Screened drug types comprise: bone morphogenetic protein-4 formation inhibitor, bone morphogenetic protein-4 antagonistic, bone morphogenetic protein-4 receptor antagonists and bone morphogenetic protein-4 downstream signal antagonistic. The invention also relates to an application of the drugs in preparation of medicines for resisting cardiac hypertrophy, heart failure and arrhythmia. Researches have found that bone morphogenetic protein-4 can induce myocardial hypertrophy, apoptosis and cardiac fibroblast collagen secretion increase, lead to occurrence of cardiac hypertrophy, heart failure and arrhythmia. However, drugs for antagonism of bone morphogenetic protein-4 and its cell signaling pathway can be used to inhibit occurrence of cardiac hypertrophy, inhibit cardiac fibrosis and minimize occurrence of cardiac cell death and arrhythmia. The invention provides a theoretical basis for realizing high-flux medicine screening, and is of practical guiding significance.

Description

technical field [0001] The present invention relates to a new application of a protein, in particular to the application of bone morphogenetic protein-4 (bone morphogenetic protein-4) and its cell signaling pathway as a drug for screening anti-cardiac hypertrophy, anti-heart failure, and anti-cardiac fibrosis. The invention also relates to an antagonist of bone morphogenic protein-4 and / or a blocker of bone morphogenic protein-4 signaling pathway and its application in the preparation of drugs against cardiac hypertrophy, heart failure and heart fibrosis. The invention belongs to the field of biomedicine. Background technique [0002] Myocardial hypertrophy, heart failure, and arrhythmia are serious heart diseases that can lead to sudden death. About 2% of adults in developing countries suffer from heart failure, and this proportion can increase to 6-10% after the age of 65. The drugs currently used for long-term treatment of myocardial hypertrophy and heart failure are ma...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/06A61K45/00A61K31/519A61P9/04A61P9/06
Inventor 董德利孙博杨宝峰霍蓉刘惠彬
Owner HARBIN MEDICAL UNIVERSITY
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