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Application of RDH10 and/or prodrug thereof in preparation of medicine for treating and/or preventing diabetic myocardial injury

A technology of RDH10, 1.RDH10, applied in the field of gene therapy, to achieve the effect of preventing/treating diabetic myocardial injury, inhibiting cardiac dysfunction and myocardial structural remodeling, and protecting cardiac function and myocardial structure

Active Publication Date: 2022-05-10
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The content of RDH10 gene has a significant impact on cell proliferation, apoptosis and cell cycle, especially, the content of RDH10 gene will also affect some tumor diseases, such as its knockout is beneficial to the treatment of glioma diseases, etc., but At present, there is no relevant research on the effect of RDH10 gene on myocardial injury in diabetes

Method used

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  • Application of RDH10 and/or prodrug thereof in preparation of medicine for treating and/or preventing diabetic myocardial injury
  • Application of RDH10 and/or prodrug thereof in preparation of medicine for treating and/or preventing diabetic myocardial injury
  • Application of RDH10 and/or prodrug thereof in preparation of medicine for treating and/or preventing diabetic myocardial injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1 Effect of diabetic myocardial injury on the expression level of myocardial RDH10 gene

[0030] In order to verify whether diabetic myocardial injury has an effect on the expression level of myocardial RDH10 gene, type 2 diabetes model db / db mice and their littermate control db / m mice (purchased from Jiangsu Jicui Yaokang) each three, fasted for 12 hours (without water) to measure their body weight and blood sugar, and then use small animal echocardiography to detect their heart function, and finally take their myocardial tissue and extract myocardial total protein to detect RDH10 The expression is as follows:

[0031] (1) Detection of body weight and blood sugar:

[0032] 4. The body weight and blood glucose test results of mice aged 24 and 32 weeks were as follows: figure 1 As shown in A, it can be seen that the blood glucose of db / db mice at the age of 4 weeks is equal to that of db / m mice, but their body weight is higher than that of db / m mice; while the ...

Embodiment 2

[0045] Example 2 Protection of RDH10 on cardiac function in mice with diabetic myocardial injury

[0046] 1. Experiment preparation

[0047] (1) Experimental materials:

[0048] 1) 30 type 2 diabetes model db / db mice at the 8th week after the blood sugar stably increased, and 10 db / m mice at the 8th week after the stably increased blood sugar in the same littermate (purchased from Jiangsu Jizhuyao Kang);

[0049] 2) Recombinant RDH10 overexpression type 9 adeno-associated virus, recombinant GFP control type 9 adeno-associated virus (purchased from Shanghai Hanheng Biotechnology Co., Ltd.);

[0050] Among them, the 16-week-old mice were defined as the 8th week after the blood glucose level increased steadily.

[0051] (2) Experimental grouping:

[0052] Thirty type 2 diabetes model db / db mice were randomly divided into three groups: 1) through the tail vein injection of recombinant RDH10 overexpressing adeno-associated virus type 9 (the virus injection volume was 0.8×10 11...

Embodiment 3

[0062] Example 3 Protection of RDH10 on myocardial structure in diabetic myocardial injury mice

[0063] (1) Preparation of heart paraffin sections:

[0064] After the remaining mice in Example 2 reached the end point of the experiment (28 weeks of stable increase in blood sugar), they were fasted 12 hours in advance without food or water. After fasting, the mouse was anesthetized with pentobarbital, the chest was opened with ophthalmological scissors, the right atrial appendage was cut open, and sterile PBS was perfused from the left ventricle of the mouse with a syringe until the blood flowed out. Finally, cut out the heart, rinse with PBS until there is no blood stain, and fix with 4% paraformaldehyde for 16h. The next day, wash with PBS 3 times, 30 minutes each time; 25% ethanol, 50% ethanol, 75% ethanol, 90% ethanol, absolute ethanol (I), absolute ethanol (II) gradient dehydration, each 30 minutes; Toluene (I) and xylene (II) each for 15 minutes; paraffin (I) and paraff...

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Abstract

The invention provides application of RDH10 and / or a prodrug thereof in preparation of a medicine for treating and / or preventing diabetic myocardial injury. Experimental results show that along with development of diabetic myocardial injury, the myocardial RDH10 gene expression level is in a trend of increasing and then decreasing, and injection of RDH10 overexpression adeno-associated virus can restore the myocardial RDH10 expression of a diabetic patient to a healthy level, and the recovery of the level can effectively protect the cardiac function and myocardial structure of the diabetic patient, so that the myocardial RDH10 gene expression level is improved. The cardiac dysfunction and myocardial structure remodeling of the diabetic patients are delayed and / or inhibited, so that the diabetic myocardial injury is effectively prevented / treated.

Description

technical field [0001] The invention belongs to the technical field of gene therapy. More specifically, it relates to the application of RDH10 and / or its prodrug in the preparation of drugs for treating and / or preventing diabetic myocardial injury. Background technique [0002] In 1972, Rubler et al first proposed the concept of myocardial injury in type 2 diabetes, which refers to a primary myocardial injury independent of hypertension and coronary artery disease. Even in patients with type 2 diabetes without myocardial ischemia and hypertension, the heart will have obvious pathological changes characterized by cardiomyocyte hypertrophy and interstitial fibrosis, that is, myocardial injury in type 2 diabetes, which will cause left Diastolic and / or systolic dysfunction of the ventricles, eventually leading to heart failure, cardiogenic shock, and even sudden death, has become the main cause of death in diabetic patients. [0003] Retinol dehydrogenase 10 (RDH10) is a membe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/44A61K45/06A61P3/10A61P9/00
CPCA61K38/443A61K45/06A61P3/10A61P9/00Y02A50/30
Inventor 蔡卫斌吴燕笛
Owner SUN YAT SEN UNIV
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