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Application of integrin alpha1beta1 inhibitor in preparation of medicine for preventing or treating aortic diseases

An integrin and inhibitor technology, applied in the preparation of drugs for the prevention or treatment of aortic disease, in the field of integrin α1β1 inhibitors, which can solve the poor prognosis of TAA patients and other problems

Pending Publication Date: 2020-04-10
SHANGHAI CHANGHAI HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Prophylactic resection can be used to prevent long-term complications such as dissection or rupture, but patients with TAA have a poor prognosis (64% five-year survival rate after surgery)

Method used

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  • Application of integrin alpha1beta1 inhibitor in preparation of medicine for preventing or treating aortic diseases
  • Application of integrin alpha1beta1 inhibitor in preparation of medicine for preventing or treating aortic diseases
  • Application of integrin alpha1beta1 inhibitor in preparation of medicine for preventing or treating aortic diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0075] Example 1: Collection of specimens from patients with thoracic aortic aneurysm and the expression level of integrin α1β1

[0076]From December 2017 to December 2018, 21 cases of thoracic aortic tissue were obtained from intraoperative resected blood vessel specimens of patients undergoing surgery for thoracic aortic aneurysm in the Department of Thoracic and Cardiovascular Surgery of Changhai Hospital, and 9 cases of normal control group were obtained from organ donations By. After taking the material, store it in liquid nitrogen, take a 1cm-sized tissue and fix it with 4% paraformaldehyde, embed it in wax block, perform histochemical staining and immunohistochemical staining, extract tissue sample RNA for quantitative PCR, and extract tissue protein for Western blot. The results showed that the level of integrin α1β1 in the thoracic aortic aneurysm group was significantly higher than that in the normal control group ( figure 1 A, 1B, 1C, 1D), western blot showed that...

Embodiment 2

[0077] Example 2: Establishment and verification of thoracic aortic aneurysm model

[0078] Forty-five C57BL / 6 adult male mice weighing 16-18 g were selected, and they were adaptively fed for 1 week with standard feed. Then using the digital table method, the mice were randomly divided into control group (Control, n=15), model group (TAA, n=15) and drug intervention group (TAA+Obt, n=15), regular feed and regular drinking water feeding. TAA group and TAA+Obt group were subcutaneously implanted with prepacked AngII micro slow-release pump (Alzet, 10370), and continuously released AngII 1000ng / (min Kg); 1 week later, TAA+Obt group was subcutaneously implanted with prepackaged Obtustatin micro slow-release pump, and sustained release of Obtustatin20ng / (min·Kg) (preliminary experiments showed that the levels of ITGA1 and ITGB1 in the model group increased significantly in the first week of administration). The mice were dissected after the establishment of the model, and the spe...

Embodiment 3

[0079] Example 3: Intervention of integrin α1β1 inhibitor Obtustatin on thoracic aortic aneurysm model

[0080] Application of integrin α1β1 blocker (Obtustatin) can significantly improve the degree of destruction of the aortic vessel wall. The results showed that the Obtustatin administration group significantly reduced the maximum diameter of the TAA model aortic lumen compared with the TAA model group ( image 3 A and 3B). HE&VB staining showed that compared with the model group, the morphology of the aortic tissue in the drug intervention group was also significantly improved, and Obtustatin could significantly improve the elastic fiber breakage of the aortic vessel wall ( image 3 C).

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Abstract

The invention relates to the technical field of biology, in particular to application of an integrin alpha1beta1 inhibitor in preparation of a medicine for preventing or treating aortic diseases. Theinvention reveals for the first time that the inhibitor of integrin alpha1beta1 can specifically inhibit the expansion of thoracic aortic aneurysm pipe diameter and reduce the damage of elastic fibersand reveals for the first time that the expression of integrin alpha1beta1 is closely related to aortic diseases, thereby providing a new target for the prevention and treatment of macrovascular diseases.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to the application of integrin α1β1 inhibitors in the preparation of drugs for preventing or treating aortic diseases. Background technique [0002] Thoracic aortic aneurysm (TAA) is an insidious but dangerous disease. The progression of TAA takes time but rarely shows symptoms, so it is often ignored, and eventually it is often accompanied by serious complications such as dissection or rupture, just like a "silent killer". As many as 21% of TAA patients with acute aortic events (including dissection and rupture) die before receiving treatment. Along with abdominal aortic aneurysm (AAA), aortic aneurysm is considered the 17th most common cause of death in people over the age of 65. It has been reported that the incidence of TAA is gradually increasing in the past decades. [0003] TAA can occur in any age, any gender, and people without significant cardiovascular risk factors. Curre...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61K45/00A61P35/00A61P35/04
CPCA61K38/1703A61K45/00A61P35/00A61P35/04
Inventor 王国坤姜宏雪李洋徐志云
Owner SHANGHAI CHANGHAI HOSPITAL