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Application of ribosome S6 kinase inhibitor SL0101 in preparation of drug for treating cardiovascular diseases

A kinase inhibitor and cardiovascular technology, which is applied in the field of drug preparation and can solve problems such as the unpopularization of percutaneous coronary intervention, expensive equipment, and limited efficacy of injectable kinase thrombolysis.

Inactive Publication Date: 2019-09-17
RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The reasons for this phenomenon are, first, because the equipment for percutaneous coronary intervention is expensive, and the training period for relevant medical and nuclear technicians is relatively long, resulting in the fact that percutaneous coronary intervention has not been popularized in remote rural areas
Second, the effect of thrombolytic therapy with kinase injection is limited, and a considerable number of patients with acute myocardial infarction fail to recanalize the obstructed coronary artery
[0007] As an immediate early gene, Nr4a3 plays an important role in regulating cell proliferation, differentiation, metabolism, and immune inflammation, but its function is specific to tissues and organs. There is no literature report on the role of Nr4a3 in acute myocardial infarction or after acute myocardial infarction. role in heart failure

Method used

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  • Application of ribosome S6 kinase inhibitor SL0101 in preparation of drug for treating cardiovascular diseases
  • Application of ribosome S6 kinase inhibitor SL0101 in preparation of drug for treating cardiovascular diseases
  • Application of ribosome S6 kinase inhibitor SL0101 in preparation of drug for treating cardiovascular diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] The expression of Nr4a family members (Nr4a1, Nr4a2, Nr4a3) and the expression of Nr4a3 at different time points in wild-type mice sham operation group and myocardial infarction model group.

[0062] 1. The mouse model of myocardial infarction was established by ligation of the left anterior descending coronary artery. The model operation process:

[0063] (1) Anesthesia: the mice were placed in an anesthesia induction box, anesthetized with 3% isoflurane, and the mice were anesthetized after about 5 minutes.

[0064] (2) Endotracheal intubation: the tail of the mouse was fixed with adhesive tape, and the upper incisors of the mouse were fixed on the operating table with 5-0 silk thread. Quickly insert the endotracheal tube through the glottis into the trachea accurately, and then connect the endotracheal tube to the ventilator. If the chest rise and fall of the mouse is consistent with the frequency of the ventilator, the endotracheal intubation is successful. Finally...

Embodiment 2

[0076] The expression of Nr4a family members (Nr4a1, Nr4a2, Nr4a3) and the expression of Nr4a3 at different time points after hypoxia treatment in primary cardiomyocytes.

[0077] 1. Extraction and culture of primary neonatal SD rat cardiomyocytes

[0078] (1) 10 newborn Sprague-Dawley suckling mice were sterilized with 75% alcohol, the heart was cut with ophthalmology, the blood was washed in pre-cooled PBS, and put into a 10cm petri dish filled with 10mL DMEM / F12 medium.

[0079] (2) After the hearts were removed one by one, the hearts were cut into 1-2mm3 tissue pieces. Transfer to a 50ml small beaker with a rotor, suck off the DMEM / F12, add 10ml of type II collagenase digestion solution with a concentration of 1mg / ml, and place it on a magnetic stirrer in a water bath. The rotation speed is 120 rpm, after 10 minutes of digestion, stand still for a few seconds, and discard the first digestion solution.

[0080] (3) Add 10 ml of type II collagenase digestion solution again...

Embodiment 3

[0087] The detection of myocardial infarction size, fibrosis degree, necrotic cells, apoptotic cells and cardiac function after myocardial infarction in wild-type and Nr4a3 knockout mice.

[0088] 1. Preparation of mouse myocardial infarction model: select wild-type and Nr4a3 knockout mice aged 10-12 weeks and weighing 24-28 g, and divide them into wild-type sham operation (WT sham) group and wild-type myocardial infarction operation group (WT MI), Nr4a3 knockout sham operation (Nkosham) group, Nr4a3 knockout myocardial infarction surgery group (Nko MI), 6 rats in each sham surgery group, 26-28 rats in each myocardial infarction surgery group, and the modeling method was the same as before. On the 1st and 14th day after the operation, the heart function of the mice in each group was tested with a small animal ultrasound machine. On the 14th day after the operation, the heart was embedded in paraffin, sectioned, and Masson stained to detect the size of the myocardial infarction ...

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Abstract

The invention belongs to the field of drug preparation and application, and particularly relates to application of a ribosome S6 kinase inhibitor SL0101 in the preparation of a drug for treating cardiovascular diseases. The invention aims at providing the drug for treating the cardiovascular diseases, wherein the drug contains a substance for performing treatment by taking an orphan nuclear receptor Nr4a3 as a drug target. Preferably, the effective component of the substance comprises the ribosome S6 kinase inhibitor SL0101. The application of the orphan nuclear receptor Nr4a3 as a target in the preparation of a drug for screening the cardiovascular diseases provides a very wide prospect and important significance for drug application of the ribosome S6 kinase inhibitor SL0101.

Description

technical field [0001] The invention belongs to the field of medicine preparation and application, in particular to the application of ribosomal S6 kinase inhibitor SL0101 in the preparation of medicines for treating cardiovascular diseases. Background technique [0002] According to the available statistical data, cardiovascular diseases occupy the first place in the burden of human diseases, and the incidence and mortality of acute myocardial infarction are increasing year by year. At present, the treatment of acute myocardial infarction mainly includes immediate percutaneous coronary intervention or thrombolysis with kinase injection. In addition, according to the epidemiological survey data of acute ST-segment elevation myocardial infarction in my country, as of 2011, as many as 45% of patients with acute ST-segment elevation myocardial infarction in China have not received percutaneous coronary intervention or drug dissolution. Any one of the recanalization treatments i...

Claims

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Application Information

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IPC IPC(8): A61K31/7048A61P9/10A61K49/00
CPCA61K31/7048A61K49/0008A61P9/10
Inventor 闫小响张瑞岩章航陆林
Owner RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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