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The function and application of iκb kinase ε inhibitor (sike) in the treatment of cardiac hypertrophy

A kind of myocardial hypertrophy and inhibitor technology, applied in medicine, the function and application of IκB kinase inhibitor (SIKE) in the treatment of myocardial hypertrophy The method reduces cardiovascular events and other problems, and achieves the effect of inhibiting myocardial hypertrophy and protecting cardiac function.

Active Publication Date: 2017-01-11
武汉惠康基因科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The morbidity and mortality of cardiovascular diseases continue to increase worldwide, and despite advances in treatment methods, there is still no effective way to reduce the occurrence of cardiovascular events

Method used

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  • The function and application of iκb kinase ε inhibitor (sike) in the treatment of cardiac hypertrophy
  • The function and application of iκb kinase ε inhibitor (sike) in the treatment of cardiac hypertrophy
  • The function and application of iκb kinase ε inhibitor (sike) in the treatment of cardiac hypertrophy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] [Example 1] Acquisition of cardiac hypertrophy (AB) model

[0035] 1. Grouping of experimental animals: cardiac-specific SIKE transgenic mice (TG) and non-transgenic mice (NTG), and cardiac hypertrophy model was established by aortic coarctation. They were randomly divided into 4 groups as follows: non-transgenic mice sham operation group (NTGSham) and AB operation group (NTG AB), heart-specific SIKE transgenic mice sham operation group (TG Sham) and AB operation group (TGAB).

[0036] 2. The myocardial hypertrophy model adopts aortic arch coarctation surgery, and the operation process of the model is as follows:

[0037] 2.1 Preoperative preparation

[0038] (1) Anesthesia: First weigh the mice, calculate the required amount of anesthetic (3% pentobarbital sodium) according to 90 mg / kg body weight, inject intraperitoneally, and record the injection time point. There is no obvious reaction between tail and toe pinching and the mouse is in good condition. This is the s...

Embodiment 2

[0045] [Example 2] Detection of cardiac hypertrophy and fibrosis in mouse cardiac hypertrophy (AB) model

[0046] 1. Collect materials

[0047] (1) Preliminary work: prepare in advance a urine cup filled with 20mL of 10% formaldehyde by volume, and label it (mouse number, group, type of operation and date of collection). A petri dish filled with 10% KCl solution was placed at the sampling site. Turn on the analytical balance and set it to zero for later use. Mice were then weighed and sacrificed.

[0048] (2) Material collection: Ophthalmic curved forceps clamped the vascular pedicle below the atrial appendage, cut off the heart, and quickly placed it in 10% KCl solution by mass fraction. After the heart stops beating in the diastolic phase, place it on sterilized gauze, gently squeeze the fluid in the heart cavity, dip the surface fluid dry, weigh and record, put the heart into the corresponding urine cup, fix it for 48 hours and use it for pathological testing.

[0049]...

Embodiment 3

[0060] [Example 3] Cardiac function detected by ultrasound in model mice with myocardial hypertrophy (AB)

[0061] 1 Preliminary preparation

[0062] (1) Anesthesia machine preparation: first connect the oxygen cylinder and the air inlet port on the anesthesia machine, then unscrew the sealing cap of the dosing port on the anesthesia machine, quickly add isoflurane to the safety scale, and then tighten the sealing cap. Unscrew the main valve on the oxygen cylinder, adjust the knob of the flow control valve, and maintain the outlet pressure at 0.2-0.3mPa.

[0063] (2) Preparation of the mice to be tested: After the mice to be tested were quickly anesthetized with isoflurane, the hair on the left chest area was shaved, and the head of the treated mice was inserted into the anesthetic catheter sleeve, and treated with 1.5-2.0% isoflurane Alkane maintains a stable anesthesia in mice.

[0064] 2 Cardiac function test

[0065] The mice were placed in the left decubitus or supine po...

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Abstract

The invention discloses a function and an application of an inhibitor SIKE of IkB kinase epsilon in cardiac hypertrophy, belonging to the field of functions and applications of genes. According to the function and application of the IkB kinase epsilon inhibitor (SIKE) in treating cardiac hypertrophy, an interrelation between the expression of SIKE and cardiac hypertrophy is determined; by adopting cardiac specific SIKE transgenic mice and non-GMOs (genetically modified organisms) as experimental objects, a cardiac hypertrophy disease model is simulated by virtue of a transverse aortic constriction operation; and a result shows that the SIKE gene over-expression can be used for significantly inhibiting cardiac hypertrophy and fibrosis of cardiac hypertrophy, and can be used for improving cardiac functions. Therefore, an SIKE gene can serve as a medicament target for screening medicaments which are used for protecting heart functions, and / or preventing, relieving and / or treating cardiac hypertrophy; the SIKE gene can be used as a target gene in gene therapy, can be used for designing and preparing the medicaments and / or biological reagents which are used for protecting the heart functions, and / or preventing, relieving and / or treating cardiac hypertrophy, and can provide an effective new route for treating cardiac hypertrophy.

Description

technical field [0001] The invention belongs to the field of gene function and application, and particularly relates to the function and application of an IκB kinase inhibitor (SIKE) in the treatment of cardiac hypertrophy, specifically the application in the preparation of drugs for preventing, alleviating and / or treating myocardial hypertrophy. Background technique [0002] According to the report of the World Health Organization, cardiovascular disease has become one of the global chronic non-communicable diseases that threaten human life and health. A variety of cardiovascular diseases, including hypertension, atherosclerosis, valvular heart disease, and cardiomyopathy, will progress to heart failure, which is the leading cause of hospitalization and death for most patients. Myocardial hypertrophy is the compensatory response of the heart to changes in mechanical load and neurohumoral factors. Clinical studies have shown that myocardial hypertrophy is not only an adaptiv...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61P9/00
Inventor 李红良蒋丁胜邓克穷张晓东
Owner 武汉惠康基因科技有限公司