Oligonucleotides and usage thereof in preparation of medicine for preventing and curing myocardial hypertrophy and heart failure

An oligonucleotide, myocardial hypertrophy technology, applied in the directions of drug combination, gene therapy, pharmaceutical formulation, etc., can solve the problems of ventricular remodeling and myocardial hypertrophy that have not been seen with oligonucleotide, and achieve the effect of inhibiting the occurrence and development

Inactive Publication Date: 2012-10-10
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Interestingly, the activation of many TLR receptors leads to the activation of the PI3Kα signaling pathway, which can effectively prevent pathological cardiac hypertrophy, but so far, there are no reports that oligonucleotides can improve ventricular remodeling and cardiac hypertrophy

Method used

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  • Oligonucleotides and usage thereof in preparation of medicine for preventing and curing myocardial hypertrophy and heart failure
  • Oligonucleotides and usage thereof in preparation of medicine for preventing and curing myocardial hypertrophy and heart failure
  • Oligonucleotides and usage thereof in preparation of medicine for preventing and curing myocardial hypertrophy and heart failure

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Inhibitory effect of oligonucleotide (ODN) on the mRNA expression of ANF and β-MHC during neonatal rat cardiomyocyte hypertrophy

[0047] 1 Isolation of neonatal rat cardiomyocytes, induction of cardiac hypertrophy model and treatment of oligonucleotides

[0048] (1) Instruments, equipment, reagents and materials

[0049] Low-temperature refrigerators, carbon dioxide incubators, ultra-clean benches, inverted microscopes, cell culture bottles, horizontal centrifuges, sample injectors, droppers of various specifications, etc. ODN: All were synthesized by Takara Company, OPC grade, and their phosphate backbones were all thio-modified unless otherwise specified. Dissolve it in PBS (for the recipe, refer to "Molecular Cloning Experiment Guide (Third Edition)"), and quantify with a UV spectrophotometer. Isoproterenol (isoproterenol), trypsin, collagenase type II, ITS and Laminin were purchased from Sigma. HBSS, DMEM, double antibody (PS) and FBS were purchased from Gibco. ...

Embodiment 2

[0088] Inhibitory effect of oligonucleotide (ODN) on ANF protein expression during cardiac hypertrophy

[0089] 1. Separation of neonatal rat cardiomyocytes and induction of cardiac hypertrophy: the method is the same as in Example 1, and the cells are inoculated into a culture dish covered with a 20mm cover glass.

[0090] 2. Indirect immunofluorescence detection of ANF protein expression

[0091] (1) Instruments, equipment, reagents and materials

[0092] PI (sigma), ANF monoclonal antibody (mouse) was purchased from Santa Cruz, FITC-fluorescent secondary antibody was purchased from Invitrogen, and confocal microscope (Leica, Germany).

[0093] (2) Method:

[0094] Aspirate the culture medium, add appropriate amount of PBS to wash 3 times; add 4% formaldehyde solution, fix at room temperature for 20 min; add appropriate amount of PBS to fully wash, add 0.5% Triton100, and permeabilize at -20°C for 10 min; 2% BSA for blocking for 1 h; add ANF primary antibody (1:200 diluti...

Embodiment 3

[0099] Oligonucleotide (ODN) Dose Curves for Inhibiting ANF and β-MHC Expression in Cardiac Hypertrophy Model

[0100] 1. Separation of neonatal rat cardiomyocytes and induction of cardiac hypertrophy: the method is the same as in Example 1.

[0101] In the dose curve experiment, neonatal rat cardiomyocytes were stimulated with RJL01 at a final concentration of 20, 10, 5, 2, 1, and 0.5 μg / ml respectively. PBS was added to the control group and model group, and after 12 hours of action, isoproterenol was added. to a final concentration of 10 μmol / ml, and continued to incubate for 48 h before performing subsequent experiments.

[0102] 2. Extraction, reverse transcription and real-time quantitative PCR of total RNA: the method is the same as in Example 1.

[0103] 3. Experimental results

[0104] The results showed that ODN RJL01 at a concentration of 1 μg / ml could effectively inhibit the up-regulation of the expression of ANF and β-MHC in the process of cardiac hypertrophy, a...

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Abstract

The invention belongs to the technical field of medicines, and particularly relates to 5'-AACGTT-3'-containing oligonucleotides, a functional analogue of the oligonucleotides, and usage of the oligonucleotides or the functional analogue of the oligonucleotides for preventing and curing myocardial hypertrophy and chronic heart failure. The oligonucleotides and the usage realize the function of the 5'-AACGTT-3'-containing oligonucleotides by using myocardial cells and animal hypertrophy models acknowledged in the academia at home and abroad. The experimental result shows that the 5'-AACGTT-3'-containing oligonucleotides can obviously restrain the expression of a landmark protein ANF (atrial natriuretic factor) and a beta-MHC (major histocompatibility complex) gene of the myocardial hypertrophy, and can restrain the increase of a superficial area of the myocardial cell, and the restrain function of the oligonucleotides depends on the dosage of the oligonucleotides.. In the whole experiment, the 5'-AACGTT-3'-containing oligonucleotides can obviously restrain the myocardial hypertrophy and the increase of the heart-body ratio, and the happening of myocardial necrosis can be reduced. The experiment result disclosed by the invention prompts that the 5'-AACGTT-3'-containing oligonucleotides is the medicine for effectively curing the myocardial hypertrophy and the heart failure.

Description

technical field [0001] The invention belongs to the technical field of bioengineering and biomedicine, and relates to an oligonucleotide and its application for preparing medicines for preventing and treating pathological cardiac hypertrophy and heart failure. Background technique [0002] Chronic heart failure, also known as congestive heart failure, refers to a pathological state in which the blood output from the heart is absolutely or relatively reduced due to the reduction of myocardial contractility under the premise of sufficient venous return, which cannot meet the metabolic needs of tissues and organs throughout the body. The end stage of heart disease caused by a variety of etiologies. With the change of people's living standard and lifestyle, coupled with the intensification of competition and the aging of society, the incidence of heart failure is increasing year by year. Therefore, how to prevent and treat heart failure is becoming more and more important and u...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/113A61K48/00A61P9/00A61P9/04A61P9/06
Inventor 杨亮李静唐向东
Owner NANKAI UNIV
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