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Purpose of HSP90 inhibitor in preparation of medicine for preventing and treating aortic diseases

An inhibitor, the technology of thoracic aorta, applied in the field of preparation and prevention of aortic disease drugs, HSP90 inhibitor, can solve the problem that the use of HSP90 inhibitor in aortic dissection disease has not been reported.

Inactive Publication Date: 2017-08-29
SHANGHAI CHANGHAI HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no report on the use of HSP90 inhibitors in the prevention and treatment of aortic dissection

Method used

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  • Purpose of HSP90 inhibitor in preparation of medicine for preventing and treating aortic diseases
  • Purpose of HSP90 inhibitor in preparation of medicine for preventing and treating aortic diseases
  • Purpose of HSP90 inhibitor in preparation of medicine for preventing and treating aortic diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0074] Example 1, collection of samples from patients with aortic dissection and expression level of HSP90

[0075] From September 2014 to December 2015, 20 cases of thoracic aortic tissue were collected from patients with acute Stanford type A thoracic aortic dissection in the Department of Thoracic and Cardiovascular Surgery of Changhai Hospital, and 8 cases of normal control group were used. It was taken from an autopsy patient without a history of cardiovascular disease, and the results of echocardiography confirmed that the aorta was not dilated. After the materials were collected, they were stored in liquid nitrogen. RNA was extracted from tissue samples for quantitative PCR, and tissue protein was extracted for Western blot. Tissues with a size of 1 cm were fixed with 4% paraformaldehyde, embedded in wax blocks, and subjected to histochemical staining and immunohistochemical staining. The results showed that the RNA and protein levels of HSP90 in the aortic dissection g...

Embodiment 2

[0076] Embodiment 2, aortic dissection model establishment and verification

[0077] Select 60 FVB adult male mice with a weight of 16-18 grams, and randomly divide them into blank control group, model group and drug intervention group, 20 in each group, and randomly divide them into 4 cages, 5 in each cage. mice. First, calculate the daily water intake of mice in each cage through unlimited feeding for 1 week, and then feed the mice with β-BAPN dissolved in purified water at 1 gram per kilogram of body weight per day in the model group and drug intervention group for 28 days; 28 Tail-cutting method was used to measure blood pressure two days later, and angiotensin II was buried under the mouse skin for 48 hours with a micropump at 1 microgram per minute per kilogram of body weight. During the whole experiment, the body weight of the mice was measured every day, and the diet was not restricted; the mice that died during the experiment were dissected in time, and the thoracic ...

Embodiment 3

[0078] Example 3, HSP90 inhibitor 17-DMAG intervention on aortic dissection model

[0079] During the modeling process, the mice in the drug intervention group were administered at 10 mg / kg every 2 days, the drug was dissolved in absolute ethanol, and injected subcutaneously, with the total amount of drug not exceeding 200 microliters each time. The experimental results showed that there was no death event in the mice in the drug intervention group ( Figure 4 A), and then found in the histological examination that the morphology of the unruptured aortic tissue has also been significantly improved ( Figure 5 A). The thoracoabdominal aorta was statistically analyzed separately, and it was found that the formation of thoracic aortic dissection and further rupture were significantly reduced, while drug intervention had no significant effect on the formation of abdominal aortic dissection.

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Abstract

The invention relates to the technical field of biology, in particular to a purpose of an HSP90 inhibitor in preparation of medicine for preventing and treating aortic diseases. The HSP90 inhibitor is used for preparing medicine or a reagent for preventing or treating aortic dissection. The invention also provides a method for screening potential substances for preventing or treating the aortic diseases, and a method for preventing or treating the aortic diseases of mammal. The invention discloses the purpose of the HSP90 inhibitor for specially inhibiting the aortic dissection cracking for the first time, and discloses the close relevancy of the HSP90 expression to the aortic diseases for the first time, so that a novel target point is provided for the large vessel disease prevention and treatment.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to the use of an HSP90 inhibitor in the preparation of drugs for preventing and treating aortic diseases. Background technique [0002] Aortic disease is a general term for various diseases that occur in the aorta, including aortic aneurysm, aortic dissection, and congenital aortic disease. These diseases are usually hidden, and once the symptoms appear, they are extremely dangerous, the operation is difficult, and the mortality rate remains high. Therefore, aortic disease is gradually becoming one of the major diseases that endanger human health. [0003] Thoracic aortic dissection (TAD) is the most dangerous disease among them. According to reports, the mortality rate of untreated thoracic aortic dissection within 24 hours is as high as 50%. With the improvement of diagnostic accuracy and the improvement of medical level, more patients with aortic dissection have the opportunity to b...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/395A61K45/00A61P9/00
CPCA61K31/395A61K45/00
Inventor 王国坤赵志敏李松华方敏徐志云
Owner SHANGHAI CHANGHAI HOSPITAL
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