Applications of growth hormone release hormone agonist in preparation of anti-vascular calcification drugs

A growth-stimulating hormone, anti-vascular calcification technology, applied in the fields of pharmacology and chemical biology

Active Publication Date: 2017-11-07
余红
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the use of GHRH-A r

Method used

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  • Applications of growth hormone release hormone agonist in preparation of anti-vascular calcification drugs
  • Applications of growth hormone release hormone agonist in preparation of anti-vascular calcification drugs
  • Applications of growth hormone release hormone agonist in preparation of anti-vascular calcification drugs

Examples

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Effect test

Embodiment 1

[0034] Example 1: Detection of the effect of GHRH-A on smooth muscle cell calcification in vitro

[0035] Implementation process: 6-8 week old C57BL / 6 male mice (purchased from Shanghai Slack Animal Experimental Animal Co., Ltd.) were sacrificed after isoflurane anesthesia to obtain thoracic aorta, digested by collagenase and elastase, plated and cultured, and selected The smooth muscle cells of passage 3-5 were used as experimental objects. Induction in 12-well plate, divided into: (A) control group, (B) osteogenic medium group, (C) osteogenic medium + GHRH-A group, (D) osteogenic medium + GHRH-A - GHRH-Anta. GHRH-A and GHRH-Anta were dissolved in DMSO (Sigma, USA) and stored as 1000x stock solutions. The working concentration of GHRH-A is 10nM, and the working concentration of GHRH-Anta is 100nM. After 14 days of induction, calcification staining, that is, Alizarin Red (Saiye Biotechnology, China) staining was performed and quantified. After the addition of GHRH-A, the s...

Embodiment 2

[0037] Example 2: Detection of the effect of GHRH-A on aortic calcification in vitro

[0038] Implementation process: 8-week-old C57BL / 6 wild-type mice and OPG at the same age - / - Mice (donated by Shan Pengfei’s research group at the Second Affiliated Hospital of Zhejiang University School of Medicine) were grouped as follows: (A) wild-type mice, (B) OPG - / - mouse, (C)OPG - / - mouse+GHRH-A. GHRH-A was dissolved in 0.1% DMSO+10% propylene glycol. The dosage of GHRH-A was 5 μg / d, injected subcutaneously, and intervened continuously for 4 weeks. After 4 weeks, the mice were euthanized, and blood samples and aorta were collected. The aorta was soaked in 10% paraformaldehyde for 24 hours, washed with D-PBS, and scanned by Micro-CT (YUEBO Biotechnology, China). The results showed that there was almost no calcification in the aorta of wild-type mice, while OPG - / - Significant calcified nodules were seen in mice, while in the GHRH-A group, aortic calcified nodules were reduced. ...

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Abstract

The present invention discloses a new medical use of a growth hormone release hormone (GHRH) agonist, particularly applications of a growth hormone release hormone agonist in preparation of anti-vascular calcification drugs. According to the present invention, GHRH-A can increase the cAMP level and the protein kinase A (PKA) activity in smooth muscle cells, can decrease the expression and the activity of NAPDH oxidase in smooth muscle cells, can decrease the ROS level in smooth muscle cells, can decrease the expression and the activity of Runx2 in smooth muscle cells, can decrease the expression and the activity of alkaline phosphatase (ALP) in cells, and can decrease the inorganic phosphorus content in blood so as to reduce the calcium deposition and the phosphorus deposition in aorta, reduce the activity of ALP in aorta, and achieve the purposes of treatment or prevention of vascular calcification and arteriosclerosis.

Description

technical field [0001] The invention relates to the fields of pharmacology and chemical biology, in particular to the application of growth-stimulating hormone-releasing hormone agonists in the preparation of anti-vascular calcification drugs. Background technique [0002] Vascular Calcification (VC) is a disease characterized by calcium salt deposition in the intima and media of blood vessels. It is closely related to various diseases such as atherosclerosis, diabetes and chronic kidney disease, and seriously affects the prognosis of these diseases. Early studies believed that arterial calcification is mainly passive calcium and phosphate deposition. However, with the deepening of research, it was found that there is a similarity between the process of arterial calcification and bone mineralization, not just passive calcium salt deposition, but more smooth muscle cells differentiate into osteoblast-like cells in a stressful environment, leading to Ongoing development of ca...

Claims

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Application Information

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IPC IPC(8): A61K38/27A61P9/14
CPCA61K38/27
Inventor 余红沈建AV 沙利蔡仁治
Owner 余红
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