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Application of doxycycline in the preparation of medicines for treating and/or preventing and/or alleviating and/or improving cardiomyopathy

A doxycycline and cardiomyopathy technology, applied in the field of medicine, can solve problems such as poor prognosis, high risk of sudden cardiac death, and low incidence

Active Publication Date: 2022-03-08
ACADEMY OF MILITARY MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although restrictive cardiomyopathy is far less common than other forms of cardiomyopathy, it has a poor prognosis and a high risk of sudden cardiac death

Method used

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  • Application of doxycycline in the preparation of medicines for treating and/or preventing and/or alleviating and/or improving cardiomyopathy
  • Application of doxycycline in the preparation of medicines for treating and/or preventing and/or alleviating and/or improving cardiomyopathy
  • Application of doxycycline in the preparation of medicines for treating and/or preventing and/or alleviating and/or improving cardiomyopathy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Example 1 Establishment of Cardiomyocyte-specific Hgs Gene Knockout Mice

[0059] Hgs to be kept in SPF animal house fl / fl The mice were mated with α-MHC-Cre mice to obtain F1 generation mice, and double-positive heterozygous mice were obtained through PCR identification, named α-MHC-Cre; Hgs fl / + mice. α-MHC-Cre; Hgs fl / + The mouse genome is integrated with the α-MHC-Cre-hGH target fragment (sequence shown in SEQ ID No.1), the Hgs gene on one chromosome (GenBank Accession No.NC_000077 (REGION: 120358431-120374810, Update Date 2020-09 The 843-9369 position of -22)) was replaced by the fragment shown in SEQ ID No.3, while the Hgs gene on the other chromosome was not replaced.

[0060] α-MHC-Cre; Hgs fl / + Mice and Hgs fl / fl Mice were mated to obtain F2 generation mice, and double-positive homozygous mice were obtained by PCR identification, which were named cardiomyocyte-specific Hgs gene knockout mice (α-MHC-Cre; Hgs fl / fl ), which is a mouse model of restrictive c...

Embodiment 2

[0082] Example 2 Detection of HGS protein expression level in the tissues of cardiomyocyte-specific Hgs gene knockout mice

[0083] Get the α-MHC-Cre prepared in Example 1; Hgs fl / fl Mouse (Hgs-cKO) and Hgs fl / fl Heart tissue of mice (control, Control).

[0084] Heart tissue protein extraction: Add 500 μL RIPA lysate (pre-added protease inhibitors and phosphatase inhibitors) to the centrifuge tube containing heart tissue, use a homogenizer to thoroughly homogenize the tissue, and wash the rotor with PBS during the process. The homogenized tissue was placed on ice for 10 min.

[0085] Place the centrifuge tube into a sonicator for sonication. Ultrasound program: Ultrasonic time 3min 30s, work 6s, interval 9s.

[0086] 12000r / min, centrifuge at 4°C for 20min.

[0087] The resulting supernatant was aspirated into another clean centrifuge tube, and the protein concentration was measured by the BCA method. The standard curve was obtained by using the measured standard concent...

Embodiment 3

[0099] Example 3 Phenotype Analysis of Cardiomyocyte-specific Hgs Gene Knockout Mice

[0100] α-MHC-Cre prepared in Example 1; Hgs fl / fl Mice (Hgs-cKO, 6) and Hgs fl / fl Mice (control, 6), aged 3 months, were killed by neck dislocation after weighing, and the heart was taken out. Observe the general shape of the heart, cut off the surrounding large blood vessels, weigh the heart with an electronic balance, measure the length of the tibia, and calculate the ratio of heart weight to body weight and heart weight to tibia length.

[0101] Figure 5 The results showed that the size of the heart of the Hgs-cKO mice was not significantly different from that of the control mice (Control) in terms of gross morphology, but there were many white plaques on the surface of the heart, and the length of the scale was 3mm. Figure 6 The results showed that the ratio of heart weight to body weight (HW / BW) of Hgs-cKO mice was not significantly different from that of control mice (Control), an...

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Abstract

The invention discloses the application of doxycycline in the preparation of medicines for treating and / or preventing and / or alleviating and / or improving cardiomyopathy. The present invention applies doxycycline to the treatment of cardiomyopathy, which can restore cardiac diastolic function, reduce myocardial cell apoptosis and / or alleviate myocardial fibrosis, and alleviate cardiomyopathy, such as restrictive cardiomyopathy.

Description

technical field [0001] The invention relates to the field of medicine, in particular to the application of doxycycline in the preparation of medicines for treating and / or preventing and / or alleviating and / or improving cardiomyopathy. Background technique [0002] Cardiomyopathy is a heterogeneous group of cardiomyopathy caused by various etiologies, manifested by inappropriate hypertrophy or dilation of the ventricles. Cardiomyopathy can be confined to the heart alone (primary cardiomyopathy) or part of a systemic disease (secondary cardiomyopathy) that can eventually lead to heart failure or death. Primary cardiomyopathy mainly includes hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and restrictive cardiomyopathy. Restrictive cardiomyopathy (RCM) mainly manifests as restricted ventricular filling and reduced diastolic volume, but ventricular systolic function and wall thickness are basically normal, and interstitial fib...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/65A61P9/08A61P9/00
CPCA61K31/65A61P9/08A61P9/00
Inventor 王剑李振华杨晓王添乐徐京平刘文佳
Owner ACADEMY OF MILITARY MEDICAL SCI
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