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Application of p-selectin glycoprotein ligand-1 as a target in the preparation of drugs for preventing and/or treating aneurysms

A technology for selecting proteins and glycoproteins, applied in the field of biomedicine, can solve the problems of controversial treatment of aneurysms, inability to fundamentally inhibit aneurysms, and lack of understanding of the pathogenesis and factors.

Active Publication Date: 2022-05-27
INST OF LAB ANIMAL SCI CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Disadvantages of open surgical repair and endovascular repair for aneurysm: Surgical treatment has indications, not all patients are suitable for open surgery or endovascular repair; surgical treatment is risky, and aneurysm itself is a high-risk disease. The risk is sometimes even higher than the risk caused by aneurysm complications
[0020] Existing drugs are currently concentrated in the animal test or clinical trial stage, and some drugs have produced controversial results in the clinical trial stage. By targeting inflammatory cells and inflammatory cytokines, the therapy is aimed at the terminal stage of the inflammatory response. Inflammation is not controlled from the initial stage of the inflammatory response, only to delay the weakening effect, and cannot fundamentally inhibit the occurrence of aneurysms
Protease inhibitor drugs also act on the formed protease, and cannot inhibit the initial steps of aneurysm formation, while antithrombotic drugs only inhibit aneurysms containing thrombus, and antithrombotic therapy Therapeutic effect needs to be determined by the advancement of clinical trials
Although renin-angiotensin system inhibitory drugs have been undergoing clinical trials, the results of clinical trials are not completely consistent, and their therapeutic effects on aneurysms are controversial
[0021] In summary, despite decades of research on AAA, there is a lack of understanding of the pathogenesis and factors of AAA. Therefore, it is important to elucidate the molecular basis of this disease, find new therapeutic targets, and develop drugs that effectively inhibit the development of aneurysms. Effective drugs have important practical significance for aneurysm research

Method used

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  • Application of p-selectin glycoprotein ligand-1 as a target in the preparation of drugs for preventing and/or treating aneurysms
  • Application of p-selectin glycoprotein ligand-1 as a target in the preparation of drugs for preventing and/or treating aneurysms
  • Application of p-selectin glycoprotein ligand-1 as a target in the preparation of drugs for preventing and/or treating aneurysms

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Example 1 Preparation of aneurysm mouse animal model

[0056] The present invention adopts 10-month-old PSGL-1 + / + Mice and PSGL-1 - / - Mice were given deoxycorticosterone acetate (DOCA) plus high-salt drinking water to induce aneurysm development. DOCA sustained-release tablet: 50mg, 21 days release. High salt: 0.9% NaCl plus 0.2% KCl. After the mice were anesthetized, the dorsal hair of the mice was shaved, and then all hair from the surgical site was removed using a depilatory cream. Lift the skin on the outside of the animal's neck, make an incision of the same size as the tablet, make a horizontal pocket with a pair of forceps about 2 cm outside the incision site, and place the DOCA tablet into the pocket with the forceps. The wound is closed with wound clips and the wound is sutured. Mice were fed high-salt drinking water (0.9% NaCl plus 0.2% KCl) for 3 weeks immediately after DOCA implantation.

Embodiment 2

[0057] Example 2 Ultrasonic detection of aorta inner diameter in small animals

[0058] A high-resolution ultrasound imaging system (Vevo 2100, Visualsonics, Toronto, Canada) was used to image and quantify the lumen diameter of the mouse suprarenal abdominal aorta. Mice were anesthetized by inhalation of isoflurane mixture, and VIP3000 isoflurane was used throughout the procedure, with O 2 (3-5% isoflurane / 97% O2) and isoflurane (1-3% isoflurane / 97% O) mixed with O2 by inhalation 2 ) to maintain. Remove the hair of the mice from the abdomen using a depilatory cream. Place the mouse supine on a heated table and apply warm ultrasound transmission gel to the abdomen. Ultrasound images were acquired over the entire region of the abdominal aorta and used to determine the maximum diameter of the abdominal aorta in the suprarenal region.

Embodiment 3

[0059] Example 3 Pathological Detection

[0060] 1) HE staining: The cut abdominal aorta paraffin sections were dewaxed to water, then stained with hematoxylin for 5 min, rinsed with tap water; differentiated with hydrochloric acid and ethanol for 30 sec; rinsed with running water, or returned to blue with light ammonia for 5 sec; stained with eosin for 5 min , rinsed with tap water; conventional dehydration, de-alcoholization, transparent, cover.

[0061] 2) Masson staining: The cut abdominal aorta paraffin sections were dewaxed to water treatment, reacted with Bouin solution at room temperature for one night, and then rinsed with running water; stained with celestine blue staining solution for 2 minutes, washed with water and stained with hematoxylin for 2 minutes After a little washing, the acid ethanol differentiation solution differentiated for several seconds; after rinsing with running water for 10 minutes, dye with Li Chunhong fuchsia staining solution for 10 minutes, ...

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Abstract

The invention relates to the field of biomedicine, in particular to the application of P-selectin glycoprotein ligand-1 as a target in the preparation of drugs for preventing and / or treating aneurysms. The present invention takes PSGL‑1 gene knockout mice as research objects, and by comparing with wild-type mice, it is found that the incidence of thoracic aortic aneurysm and abdominal aortic aneurysm in the PSGL‑1 gene knockout group mice are significantly reduced, collagen The deposition becomes less, the breakage of elastic fibers and the degradation of smooth muscle cells are significantly inhibited, and the infiltration of inflammatory cells is significantly reduced, and the expression of inflammatory factors, fibrosis factors and adhesion molecules is significantly inhibited. In addition, the adhesion of peripheral blood mononuclear cells to endothelial cells was significantly reduced in PSGL-1-deficient PBMCs. The present invention reveals that the deletion of PSGL-1 has the effect of inhibiting aneurysms, and provides a theoretical basis and clinical basis for the role of PSGL-1 in the study of new targets and new strategies for preventing and treating aneurysms.

Description

technical field [0001] The present invention relates to the field of biomedicine, in particular to the application of P-selectin glycoprotein ligand-1 as a target in preparing medicines for preventing and / or treating aneurysms. Background technique [0002] Aortic aneurysms can be divided into thoracic aortic aneurysms (TAA) and abdominal aortic aneurysms (AAA) according to their location. TAA occurs in people of all ages, occurs at similar rates in men and women, and is highly associated with genetic factors. In contrast, the usual occurrence of AAA is associated with aging, male sex, atherosclerosis, and smoking, but with weaker genetic associations. AAA is the most common form of aortic aneurysm, commonly found in adults over the age of 50, and occurs more frequently in men than in women. Aneurysm rupture is the most dangerous complication of abdominal aortic aneurysm and the leading cause of death in patients. Currently, open surgical repair and endovascular repair ar...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61P9/00A61P9/14
CPCA61K45/00A61P9/00A61P9/14
Inventor 杨志伟吴献贤刘星
Owner INST OF LAB ANIMAL SCI CHINESE ACAD OF MEDICAL SCI
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