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Application of Hint2 in preparation of medicine for treating or diagnosing heart failures

A technology for heart failure and purpose, applied in the field of biomedicine, can solve problems such as rising, and achieve the effect of reducing the fatality rate, improving the symptoms of patients, and improving the metabolic level of cardiomyocytes

Pending Publication Date: 2022-01-11
ZHONGSHAN HOSPITAL FUDAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In the course of research, the inventors of the present invention discovered a highly conserved dimeric protein located on the inner membrane of mitochondria—Histidine triad nucleotide-binding protein 2 (Hint2), and Through the mouse pressure load heart failure model (Transverse aortic constriction, TAC), the mouse doxorubicin heart failure model (a model used to study tumor heart disease) and human heart failure myocardial tissue experiments, it was further discovered that myocardial Hint2 Protein expression is significantly increased in heart failure, and it is verified that Hint2 is expected to be a new target for heart failure treatment. Overexpression of adeno-associated virus can play a role in the treatment of heart failure. There is no relevant technical report so far

Method used

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  • Application of Hint2 in preparation of medicine for treating or diagnosing heart failures
  • Application of Hint2 in preparation of medicine for treating or diagnosing heart failures
  • Application of Hint2 in preparation of medicine for treating or diagnosing heart failures

Examples

Experimental program
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Effect test

Embodiment 1

[0027] The establishment of embodiment 1 pressure load heart failure model

[0028] Select male mice aged 8-10 weeks to establish a pressure-loaded heart failure model by ligation of the constricted aortic arch. The steps are as follows: depilate the neck and chest of the mice, anesthetize and fix the skin, and cut the skin along the median neck incision to expose the neck to the sternum Cut the suprasternal fossa area, carefully bluntly separate the thymus tissue with micro forceps, fully expose the aortic arch and its branches (brachiocephalic trunk, left common carotid artery, left subclavian artery); carefully separate the tissue near the aortic arch, and use Pass the No. 5 silk thread through the aortic arch with a self-made hook, place the 27G needle horizontally on the aortic arch, and ligate the silk thread on the needle; check the bleeding point, suture the skin, put the mouse on the heating pad until it wakes up, and then return it to the animal room .

Embodiment 2

[0029] Example 2 Cardiac Ultrasonic Detection of Cardiac Structure and Function

[0030] The Vevo 2100 small animal ultrasound imaging system produced by Canada Visual Sonics was used for two-dimensional M-mode ultrasound detection, and the echocardiography analysis was performed on the mice in each group at baseline, 4 weeks and 8 weeks after TAC. After hair removal, the mouse was placed on a heating plate, anesthetized with 1%-2% isoflurane, and the heart rate was maintained at about 450-550 beats / min. The cardiac function (LVEF, left ventricular fractional shortening) and cardiac structure (left ventricular End-diastolic diameter / end-systolic diameter, relative to wall thickness).

Embodiment 3W

[0031] Embodiment 3WGA staining

[0032] The mice in each group were anesthetized by intraperitoneal injection of pentobarbital sodium and then sacrificed. The heart was flushed with normal saline. After the heart was taken out, it was cut into slices of about 1 mm along the plane of the papillary muscle of the heart. They were fixed in 10% neutral formaldehyde at room temperature for 24 Hour. Paraffin-embedded sections were cut into 4 μm thickness, placed on glass slides for Sirius red and WGA staining, and evaluated cardiac fibrosis and cardiomyocyte hypertrophy.

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Abstract

The invention discloses application of Hint2 in preparation of a medicine for treating or diagnosing heart failures, belonging to the technical field of biological medicine. The application, particularly the application of the Hint2 in preparation of the medicine for treating or diagnosing a heart failure caused by tumor heart disease or a heart failure caused by hypertension, comprises the step of applying an effective amount of the medicine to myocardial tissue of a subject to intervene expression of the Hint2 and influence mitochondrial metabolism so as to improve myocardial tissue metabolism of the subject. According to the invention, the Hint2 is provided as a novel target for treating the heart failure for the first time, the recombinant 9-type adeno-associated virus overexpressed by the human Hint2 gene is used for treating heart failure, and the prognosis of heart failure is predicted by detecting the expression level of the Hint2 of a patient with a heart failure, so a new thought is provided for clinical treatment or diagnosis of heart failures.

Description

technical field [0001] The invention belongs to the technical field of biomedicine and relates to the use of Hint2 in the preparation of medicines for treating or diagnosing heart failure, especially the use of Hint2 in the preparation of medicines for treating or diagnosing heart failure caused by tumor heart disease or heart failure caused by hypertension. Background technique [0002] Heart failure (heart failure) is the end stage of various heart diseases. Due to the low control rate of hypertension, the increased disease burden of chronic diseases such as coronary heart disease and diabetes, and the use of chemotherapy drugs including doxorubicin The incidence of heart failure caused by the above factors is increasing year by year. In my country alone, about 13.7 million people over the age of 35 suffer from heart failure. The high prevalence, high mortality and rehospitalization rate of heart failure have caused huge clinical and economic burdens worldwide. Although t...

Claims

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Application Information

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IPC IPC(8): G01N33/68C12N15/864C12N5/10A61K35/761A61P9/04
CPCG01N33/6893C07K14/47C12N15/86A61K35/761A61P9/04C12N2750/14143
Inventor 葛均波蒋昊孙爱军章金延张倍健贾代乐
Owner ZHONGSHAN HOSPITAL FUDAN UNIV
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