阅读说明：本技术 N6022在预防和治疗主动脉夹层和主动脉瘤中的应用 (Application of N6022 in prevention and treatment of aortic dissection and aortic aneurysm ) 是由 季勇 谢利平 张曦月 缪青 张益华 高婕 于 2020-04-24 设计创作，主要内容包括：N6022在治疗主动脉夹层和主动脉瘤中的应用,涉及在心血管领域。在主动脉夹层及主动脉瘤小鼠模型中,尾静脉注射N6022能抑制主动脉的扩张,减少动脉夹层和主动脉瘤的发生率及死亡率；且N6022可以减少主动脉瘤体的破裂,抑制管腔内壁内血肿的发生及血管壁过度胶原的沉积,维持血管壁弹力纤维的完整性,治疗主动脉夹层和瘤疾病。本发明开拓了N6022一个新的应用领域,对于防治主动脉夹层和主动脉瘤疾病,改善血管病变状况提供了有意义的参考。(The application of N6022 in the treatment of aortic dissection and aortic aneurysm relates to the field of cardiovascular diseases. In aortic dissection and aortic aneurysm mouse models, tail vein injection of N6022 can inhibit aortic expansion, and reduce incidence and mortality of aortic dissection and aortic aneurysm; and N6022 can reduce rupture of aortic aneurysm, inhibit hematoma in lumen and excessive collagen deposition in vessel wall, maintain integrity of elastic fiber in vessel wall, and treat aortic dissection and aneurysm diseases. The invention develops a new application field of N6022, and provides meaningful reference for preventing and treating aortic dissection and aortic aneurysm diseases and improving the condition of vasculopathy.)

Use of N6022 or a derivative thereof for the preparation of a medicament for the treatment of aortic dissection and aortic aneurysm.

Use of N6022 or a derivative thereof for the preparation of a medicament for the prevention of aortic dissection and aortic aneurysm.

3. A preventive or remedy for aortic dissection and aortic aneurysm, characterized by comprising N6022 or a derivative thereof as an active ingredient.

Technical Field

The invention belongs to the technical field of aortic dissection and aortic aneurysm treatment, and particularly relates to application of a nitrosoglutathione reductase (GSNOR) inhibitor N6022 in prevention and treatment of aortic dissection and aortic aneurysm.

Background

Aortic dissection and aortic aneurysm are the most serious large vessel disease in aortic disease, the pathological manifestation of which is the progressive dilatation of aorta, and the characteristics of occult pathogenesis and rupture death are great public health problems. Abnormal structural changes such as degeneration and degeneration of blood vessels occur in the middle layer of blood vessels in early stage of diseases, and specific symptoms or signs are not usually shown before the blood vessels are ruptured; with the increase of the tumor diameter, the fracture probability is obviously increased, and the rupture is accompanied by the formation of intimal tear and false cavity, the death rate of a patient after the tumor is fractured is up to 90 percent, so that the early prevention and treatment before the fracture is particularly important.

At present, the treatment method aiming at the aortic dissection and the aortic aneurysm is still mainly operated, but the incidence rate and the mortality rate of serious complications such as large operative trauma, paraplegia and the like are as high as 17 percent and 26 percent; and there is controversy as to whether surgery is required for patients with aortic diameters less than 5.0 cm. The clinical drugs comprise adrenergic beta receptor blocking drugs, angiotensin converting enzyme inhibitors, statins and the like, the drugs can only slow down the disease process by controlling indexes such as blood pressure, heart rate, blood fat and the like, and have a plurality of adverse reactions and side effects, and specific drugs for prevention and treatment are not found. Therefore, there is a need for safer and more effective drugs for prevention and treatment of aortic aneurysms and aortic dissections.

Nitrosoglutathione reductase (GSNOR) is a specific protease in the alcohol dehydrogenase family, and its main role in the cell is to regulate the metabolism of nitrosoglutathione (S-nitrosoglutathione, GSNO), which in turn affects the steady-state regulation of intracellular Nitric Oxide (NO). Nitrosoglutathione reductase (GSNOR) inhibitor N6022 is a specific reversible nitrosoglutathione reductase inhibitor, studies have shown that N6022 is effective in improving asthma and allergic airway inflammation, and N6022 has been completed as a first and second phase clinical trial for treating chronic asthma and cystic fibrosis. Recently, N6022 has been reported to have certain curative effect on autoimmune encephalomyelitis (EAE). However, whether N6022 can improve aortic dissection and aortic aneurysm and the mechanism thereof is not researched and reported at present.

Disclosure of Invention

The technical problem to be solved is as follows: the invention provides an application of N6022 in prevention and treatment of aortic dissection and aortic aneurysm, which effectively improves aortic dissection and aortic aneurysm diseases through the inhibition effect on GSNOR. The method comprises injecting N6022 into tail vein of mice of aortic dissection and aortic aneurysm model to prevent occurrence of aortic dissection and aortic aneurysm and reduce death rate of aortic dissection and aortic aneurysm.

The technical scheme is as follows: the application of N6022 or its derivative in preparing medicine for treating aortic dissection and aortic aneurysm is provided.

The application of N6022 or derivatives thereof in preparing medicaments for preventing aortic dissection and aortic aneurysm.

The medicine for preventing and treating aortic dissection and aortic aneurysm contains N6022 or its derivative as effective component.

Has the advantages that: the N6022 can inhibit pathological expansion of aorta by intravenous injection, and reduce incidence and mortality of arterial dissection and aortic aneurysm; and N6022 can reduce rupture of aortic aneurysm, reduce hematoma in lumen wall and excessive collagen deposition in vessel wall, maintain integrity of elastic fiber in vessel wall, and treat aortic dissection and aortic aneurysm diseases. The invention develops a new application field of N6022, and provides meaningful reference for preventing and treating aortic dissection and aortic aneurysm diseases and improving the condition of vasculopathy.

Drawings

FIG. 1 model of aortic dissection mice constructed by BAPN drinking water, with tail vein injection of control solvents DMSO, and N6022(0.01mg/kg/day, 0.1mg/kg/day, 1mg/kg/day), respectively, where A: observing and counting the death rate graph of the aortic dissection during the modeling period; b: aorta general view.

Fig. 2 is a graph showing the incidence and rupture rate of aortic dissection observed and counted during the molding process.

FIG. 3A model of an aortic aneurysm mouse constructed by an AngII osmotic micropump, followed by tail vein injection of DMSO, a control solvent, and N6022(0.1mg/kg/day), respectively, wherein A: detecting the inner diameter of the aorta and the tumor formation of the mouse by vascular ultrasound; b: mouse aortic inner diameter statistical plot, < 0.05; c: aorta general view.

Fig. 4 is a schematic diagram showing the maximum outer diameter of a blood vessel measured by a vernier caliper <0.05, by peeling the aorta of a mouse by a micromachine, measuring the ratio of the weight of the aorta to the weight of the mouse by an analytical balance.

FIG. 5 is a schematic representation of the morphology of aortic aneurysms detected by paraffin-embedded section of aorta, H & E tissue staining.

FIG. 6 is a schematic representation of aortic wall collagen deposition by paraffin-embedded section of aorta and Masson tissue staining.

FIG. 7 is a schematic diagram of the detection of elastic fiber breakage by aortic glutaraldehyde fixation, dehydration, sectioning, and projection electron microscopy.

Detailed Description

The following examples further illustrate the present invention but are not to be construed as limiting the invention. Modifications and substitutions to methods, procedures, or conditions of the invention may be made without departing from the spirit and substance of the invention. Unless otherwise specified, the technical means used in the examples are conventional means well known to those skilled in the art. The reagents and materials used in the following examples are all commercially available products. N6022 used in the examples is a commercially available product, purchased from seleck. cn, having the formula: