Application of chaetocin in preparation of drugs for preventing and treating hypoxic pulmonary hypertension

A technology of pulmonary arterial hypertension and chaetokin, which is applied in the field of biomedicine, can solve the problems of ineffective inhibition, achieve strong pharmacological effects, reduce pulmonary artery pressure, and reduce pressure load

Inactive Publication Date: 2018-06-12
ARMY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Currently, the main treatments for pulmonary arterial hypertension include oxygen therapy, vasodilators (such as prostaglandins, endothelin receptor antagonists, etc.) and histone deacetylase inhibitors, which have improved the survival rate of patients to a certain extent. However, none of them can effectively inhibit and reverse the occurrence of pulmonary vascular remodeling

Method used

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  • Application of chaetocin in preparation of drugs for preventing and treating hypoxic pulmonary hypertension
  • Application of chaetocin in preparation of drugs for preventing and treating hypoxic pulmonary hypertension
  • Application of chaetocin in preparation of drugs for preventing and treating hypoxic pulmonary hypertension

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1: Observation of the protective effect of Mao Kesu on hypoxia-induced pulmonary hypertension

[0032] Chaetocin was purchased from sigma company, product number C9492.

[0033] Preparation method: chaetocin was prepared into a 2mg / 1ml stock solution with dimethyl sulfoxide, and diluted with normal saline to a final concentration of 0.1ug / ul before use.

[0034] experimental method:

[0035] SPF grade male C57BL / 6 mice (purchased from the Animal Institute of the Third Military Medical University, the same below) were selected and randomly divided into three groups for 6-8 weeks: normoxia group (Sham), hypoxia group (Sham+Hypoxia), Chaetocin group (Cha+Hypoxia, 0.5mg / kg / 2d), 10 rats in each group. The mouse model of hypoxic pulmonary hypertension (HPH) was reproduced by the continuous hypobaric hypoxia method, that is, the mice in the hypoxic group were placed in a hypobaric hypoxic cabin (pressure: 380mm Hg) at a simulated altitude of 5000m for 28 days of cont...

Embodiment 2

[0042] Example 2: Regulatory Effect of Chaetin on Smooth Muscle Cell Apoptosis under Chronic Hypoxia

[0043] Chaetocin was purchased from sigma company, product number C9492.

[0044] Preparation method: chaetocin is prepared into 1mM / L stock solution with dimethyl sulfoxide, and diluted with medium before use to a final concentration of 50-100uM / L.

[0045] experimental method:

[0046] Human primary pulmonary artery smooth muscle cells (Human pulmonary arterial endothelial cells, HPASMC) were purchased from Invitrogen, USA, and cultured with HPASMC-specific culture medium, and the cells were placed at 37°C, 5% CO 2 cultured in a cell culture incubator. Cells were subcultured when they reached 90% confluence, and cells in logarithmic growth phase were selected for experiments. When the cells are subjected to hypoxic treatment, place the inoculated cells in a 2 and CO 2 in the tri-gas incubator, and the O 2 The concentration was set at 1% (5% CO 2 , 94%N 2 ), and remo...

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Abstract

The invention discloses application of chaetocin in preparation of drugs for preventing and treating hypoxic pulmonary hypertension. Test researches show that when the chaetocin is used for preparingthe drugs for preventing and treating hypoxic pulmonary hypertension, pulmonary arterial pressure can be reduced remarkably, pulmonary vascular remodeling caused by chronic hypoxia is improved, pressure load of the ventriculus dexter is relieved, cardiac hypertrophy and ventricular remodeling are improved, heart failure is delayed, it shows great effect of preventing and treating hypoxic pulmonaryhypertension, in an experiment process, obvious adverse reactions are not seen, and the drugs are expected to be developed into a new-generation safe and effective drug for preventing and treating pulmonary hypertension.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of chaetocin in the preparation of drugs for preventing and treating hypoxic pulmonary hypertension. Background technique [0002] Pulmonary arterial hypertension (PAH) refers to a hemodynamic and pathophysiological state in which pulmonary artery pressure rises above a certain threshold, which can lead to right heart failure. It can be an independent disease or a complication. It can also be a syndrome. The hemodynamic diagnostic standard is that the mean pulmonary artery pressure measured by right heart catheterization is greater than 25mmHg at resting state at sea level. Its main feature is a progressive increase in pulmonary vascular resistance, which eventually leads to right heart failure and even death. The main manifestations of pulmonary hypertension are shortness of breath, shortness of breath, fatigue, chest pain, depressed dry cough, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/548A61P11/00A61P9/12
CPCA61K31/548
Inventor 陈德伟高钰琪徐刚王授衔
Owner ARMY MEDICAL UNIV
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