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Application of IRX4 and inducer thereof in screening/preparing medicine for protecting heart

An inducer and drug technology, which can be used in drug combinations, pharmaceutical formulations, cardiovascular system diseases, etc., can solve the problems of increased QT dispersion and increased outflow gradient, so as to inhibit myocardial fibrosis, improve cardiac function, and protect hypertrophy. effects of cardiomyopathy

Pending Publication Date: 2021-02-12
WUHAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Clinical studies have found that there is an association between Irx4 gene mutations and hypertrophic cardiomyopathy. Four polymorphisms have been found in the IRX4 gene. The A381>G polymorphism AA genotype has a higher maximum left ventricular outflow tract gradient. and prolonged corrected QT dispersion, suggesting that IRX4 may mediate septal thickness leading to increased corrected QT dispersion and increased efflux gradient

Method used

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  • Application of IRX4 and inducer thereof in screening/preparing medicine for protecting heart
  • Application of IRX4 and inducer thereof in screening/preparing medicine for protecting heart
  • Application of IRX4 and inducer thereof in screening/preparing medicine for protecting heart

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Experimental program
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Effect test

Embodiment 1

[0036] According to the method of gene mouse construction, mice with specific overexpression of IRX4 cardiomyocytes were established. The expression of IRX4 was verified by WB. The result is as figure 1 As shown, IRX4 overexpression mice can be seen, and the expression of IRX4 is significantly increased, indicating that the gene mouse was successfully constructed.

Embodiment 2

[0038] IRX4 overexpression significantly ameliorated AB-induced cardiac hypertrophy, fibrosis and deterioration of cardiac function

[0039] 1. Experimental grouping: WT+sham group, WT+AB group, TG-IRX4+sham group, TG-IRX4+AB

[0040] 2. Establishment and detection of myocardial hypertrophy model:

[0041] The mice in group AB were given constriction of the aortic arch (AB). Specific methods: ① anesthetize, weigh and anesthetize the mouse with 3% pentobarbital sodium; ② skin preparation: remove the hair in the operation area; ③ endotracheal intubation; ④ ligation of the descending branch of the aortic arch: the mouse takes the right lateral position , the skin was disinfected, the chest was opened, the free aortic arch was lowered, and the vascular disease was ligated with a 7-0 surgical front line, after which the chest was closed and the skin was sutured.

[0042] Mice in the Sham group: after freeing the descending aorta, only the thread was threaded without ligation, and...

Embodiment 3

[0044] Four weeks after operation, the cardiac function, myocardial hypertrophy and fibrosis of mice in each group were measured, and the effect of IRX4 gene overexpression on aortic arch administration-induced myocardial hypertrophy was studied.

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Abstract

The invention discloses an IRX4 and application of an inducer of the IRX4 in screening / preparing a medicine for protecting the heart. Wild mice and heart-specific IRX4 gene overexpression mice are selected as experimental subjects, an aortic arch constriction operation is performed by an operation group to construct a myocardial hypertrophy model, and myocardial hypertrophy, fibrosis and cardiac functions of each group of mice are measured in four weeks after the operation so as to research the functions of the IRX4 gene. Results show that IRX4 has the effects of inhibiting cardiac hypertrophy, resisting fibrosis and improving cardiac functions; therefore, IRX4 can be used for screening drugs for protecting the cardiac function, resisting myocardial fibrosis and / or preventing, relieving and / or treating myocardial hypertrophy and related diseases, and can be used for preparing drugs for protecting the cardiac function, resisting myocardial fibrosis and / or preventing, relieving and / or treating myocardial hypertrophy. The invention provides an effective new way for treating myocardial hypertrophy.

Description

technical field [0001] The invention belongs to the field of gene function and application, in particular to an application of IRX4 and its inducer in screening / preparing heart-protecting drugs. Background technique [0002] Myocardial hypertrophy is a common pathological process of the occurrence and development of various cardiovascular diseases such as hypertension, vascular disease and chronic heart failure. a compensatory response. Long-term stimulation can lead to pathological myocardial hypertrophy, which is mainly characterized by increased myocardial cell volume, increased protein synthesis, increased extracellular matrix, and fibrosis, which eventually lead to dilated cardiomyopathy, ventricular arrhythmia, myocardial ischemia, Heart failure and even sudden death. Myocardial hypertrophy has become an independent risk factor and a signal of poor prognosis for various cardiovascular diseases such as heart failure. Cardiovascular diseases such as heart failure cause...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61P9/00
CPCA61K45/00A61P9/00
Inventor 唐其柱张楠李文静廖海含周子颖牟山琪丁雯
Owner WUHAN UNIV
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