CN108498521B

CN108498521B - Application of cycloastragenol in preparation of medicine for inhibiting abdominal aortic aneurysm

Info

Publication number: CN108498521B
Application number: CN201710105881.7A
Authority: CN
Inventors: 祁荣; 王云霞
Original assignee: Peking University
Current assignee: Peking University
Priority date: 2017-02-24
Filing date: 2017-02-24
Publication date: 2020-05-05
Anticipated expiration: 2037-02-24
Also published as: CN108498521A

Abstract

The invention discloses an application of cycloastragenol in preparing a medicament for inhibiting abdominal aortic aneurysm. The invention provides an application of cycloastragenol, which is (a1) and/or (a 2): (a1) preparing a product for preventing and/or treating abdominal aortic aneurysm; (a2) preventing and/or treating abdominal aortic aneurysm. The invention also provides a medicament for preventing and/or treating abdominal aortic aneurysm, which comprises cycloastragenol as an active ingredient. The medicament for inhibiting the abdominal aortic aneurysm is safe, low in toxicity and strong in pharmacological action; the raw materials are wide in source and low in price, and can be obtained by hydrolyzing astragalus extract astragaloside IV; the preparation cost is low, the process is simple, and the yield is high; and has definite curative effect. The invention provides a new medicine source for preventing, diagnosing, detecting, protecting, treating and researching the abdominal aortic aneurysm diseases, is easy to popularize and apply, and can generate great social benefits and economic benefits in a short time.

Description

Application of cycloastragenol in preparation of medicine for inhibiting abdominal aortic aneurysm

Technical Field

The invention relates to an application of cycloastragenol in preparing a medicament for inhibiting abdominal aortic aneurysm.

Background

Abdominal Aortic Aneurysm (AAA) is a serious progressive degenerative disease, manifested by dilation of the abdominal aorta with degradation of the arterial wall extracellular matrix and development of chronic inflammation. AAA has a morbidity rate of up to 8% in older men over 65 years of age, with men being slightly older than women and being the 13 th leading cause of death in our country. Smoking, advanced age and atherosclerosis have been identified as the most major risk factors for AAA induction. Most patients with AAA have no obvious clinical symptoms except occasional abdominal pain, and few patients have a tumor body which is already ruptured when the patients find the disease, the death rate after rupture is up to 80 percent, and the patients have serious harm to the health and life of the human bodies.

Clinically, AAA is considered to occur when the abdominal aorta diameter exceeds 50% of the normal diameter or > 3.0 cm. When the tumor diameter is larger than 5.5cm, the large AAA is obtained, and the small AAA is obtained when the tumor diameter is between 3.0 and 5.5 cm. Currently, the clinical treatment for AAA depends on the diameter, and when the diameter is more than 5.5cm, the operation treatment is adopted, but the large AAA only accounts for about 10 percent. Most AAA belongs to small AAA, and routine B-mode ultrasound monitoring is recommended clinically. However, such small AAA expands at a rate of 4mm per year, and finally reaches about 5cm in 3-5 years, and even breaks occur, causing death of the patient, so the treatment of small AAA is an important research topic, and finding effective drugs for inhibiting the expansion of small AAA has very important clinical significance for reducing the risk of breaking and the death rate of the patient.

Studies have shown that the onset of AAA is associated with chronic transmural inflammation of the arterial wall, degradation of extracellular matrix, and reduction and apoptosis of smooth muscle cells. Among them, the occurrence of inflammation is considered as an initiation factor of AAA occurrence and development, and inflammatory cells mainly including macrophages infiltrate and activate in the arterial wall, and then secrete a large amount of proinflammatory cytokines, thereby exacerbating the inflammatory response of the arterial wall. In addition, macrophages also secrete matrix metalloproteinases that degrade the extracellular matrix of the arterial wall, reducing the elasticity of the arterial wall. Meanwhile, the apoptosis of smooth muscle cells of the artery wall can be caused by the inflammation, the apoptotic smooth muscle cells can secrete proinflammatory cytokines, monocyte chemotactic protein and the like, the cascade reaction of the inflammation is triggered, and the infiltration of inflammatory cells and the secretion of matrix metalloproteinase are further recruited. This forms a vicious circle that ultimately leads to progressive degradation of the extracellular matrix of the arterial wall. In addition, oxidative stress synergizes with inflammation to exacerbate the development and progression of AAA.

From the pathogenesis of AAA, the drug therapy targets are mainly focused on anti-inflammation, anti-oxidation, and inhibition of matrix metalloproteinase activity. In recent years, drugs for clinically treating AAA mainly include statins represented by simvastatin, hypotensive drugs such as angiotensin converting enzyme inhibitors and angiotensin receptor blockers, antibiotics represented by doxycycline, and the like. However, there are some research reports that these drugs have problems of uncertain curative effect or certain toxic and side effects. Therefore, effective clinical medicines are lacked for the prevention and treatment of the small abdominal aortic aneurysm at present, and the development of new medicines with definite curative effect and small side effect has great clinical significance for the prevention and treatment of the abdominal aortic aneurysm.

Cycloastragenol (CAG) is an active aglycone of astragaloside and research shows that cycloastragenol has wide effects of resisting inflammation, resisting oxidative stress, inhibiting endoplasmic reticulum stress, resisting aging, resisting virus, resisting hyperlipidemia and the like. There is no report on the anti-AAA activity of cycloastragenol.

Disclosure of Invention

The invention aims to provide application of cycloastragenol in preparing a medicament for inhibiting abdominal aortic aneurysm.

The invention provides an application of cycloastragenol, which is (a1) and/or (a 2):

(a1) preparing a product for preventing and/or treating abdominal aortic aneurysm;

(a2) preventing and/or treating abdominal aortic aneurysm.

The invention also protects the application of the cycloastragenol, which is at least one of the following (b1) - (b 12):

(b1) preparing a product for inhibiting the rupture of the abdominal aorta elastic plate;

(b2) preparing a product for inhibiting the thickening of the adventitia of the abdominal aorta;

(b3) preparing a product for inhibiting the abdominal aorta vasodilatation;

(b4) preparing a product for inhibiting the rupture of an abdominal aorta elastic plate of an abdominal aortic aneurysm patient;

(b5) preparing a product for inhibiting the thickening of the outer membrane of the abdominal aorta of a patient with abdominal aortic aneurysm;

(b6) preparing a product for inhibiting the abdominal aortic vasodilation of an abdominal aortic aneurysm patient;

(b7) inhibiting the rupture of the abdominal aorta elastic plate;

(b8) inhibiting thickening of the abdominal aorta adventitia;

(b9) inhibit abdominal aortic vasodilation;

(b10) inhibiting rupture of an abdominal aorta elastic plate of an abdominal aortic aneurysm patient;

(b11) inhibiting the thickening of the outer aorta adventitia of a patient with abdominal aortic aneurysm;

(b12) inhibit the abdominal aortic vessel dilation of patients with abdominal aortic aneurysm.

The invention also protects the application of the cycloastragenol, which is at least one of the following (c1) - (c 16):

(c1) preparing a product for inhibiting oxidative stress of vascular smooth muscle cells;

(c2) preparing a product for inhibiting vascular smooth muscle cell inflammatory response;

(c3) preparing a product for inhibiting oxidative stress of the abdominal aorta;

(c4) preparing a product for inhibiting an abdominal aorta inflammatory response;

(c5) preparing a product for inhibiting vascular smooth muscle cell oxidative stress of patients with abdominal aortic aneurysm;

(c6) preparing a product for inhibiting vascular smooth muscle cell inflammatory response of patients with abdominal aortic aneurysm;

(c7) preparing a product for inhibiting the oxidative stress of the abdominal aorta of a patient with abdominal aortic aneurysm;

(c8) preparing a product for inhibiting an abdominal aortic inflammation reaction of a patient with abdominal aortic aneurysm;

(c9) inhibiting vascular smooth muscle cell oxidative stress;

(c10) inhibiting vascular smooth muscle cell inflammatory responses;

(c11) inhibiting abdominal aortic oxidative stress;

(c12) inhibiting an abdominal aorta inflammatory response;

(c13) inhibiting vascular smooth muscle cell oxidative stress in patients with abdominal aortic aneurysm;

(c14) inhibiting vascular smooth muscle cell inflammatory response of patients with abdominal aortic aneurysm;

(c15) inhibiting abdominal aortic oxidative stress in patients with abdominal aortic aneurysm;

(c16) inhibiting the inflammation reaction of abdominal aorta of patients with abdominal aortic aneurysm.

The invention also protects the application of the cycloastragenol, which is at least one of the following (d1) - (d 8):

(d1) preparing a product for promoting the synthesis of vascular smooth muscle cell elastin;

(d2) preparing a product for promoting the synthesis of the abdominal aorta elastin;

(d3) preparing a product for promoting the synthesis of vascular smooth muscle cell elastin of patients with abdominal aortic aneurysm;

(d4) preparing a product for promoting the synthesis of the abdominal aorta elastin of patients with abdominal aortic aneurysm;

(d5) promoting the synthesis of vascular smooth muscle cell elastin;

(d6) promoting the synthesis of abdominal aorta elastin;

(d7) promoting the synthesis of vascular smooth muscle cell elastin of patients with abdominal aortic aneurysm;

(d8) promote the synthesis of the abdominal aorta elastin of patients with abdominal aortic aneurysm.

The invention also protects a product, the active ingredient of which is cycloastragenol; the product is used for preventing and/or treating abdominal aortic aneurysm.

The invention also protects a product, the active ingredient of which is cycloastragenol; the product has at least one of the following uses (e1) - (e 6):

(e1) inhibiting the rupture of the abdominal aorta elastic plate;

(e2) inhibiting thickening of the abdominal aorta adventitia;

(e3) inhibit abdominal aortic vasodilation;

(e4) inhibiting rupture of an abdominal aorta elastic plate of an abdominal aortic aneurysm patient;

(e5) inhibiting the thickening of the outer aorta adventitia of a patient with abdominal aortic aneurysm;

(e6) inhibit the abdominal aortic vessel dilation of patients with abdominal aortic aneurysm.

The invention also protects a product, the active ingredient of which is cycloastragenol; the product has at least one of the following applications (f1) - (f 8):

(f1) inhibiting vascular smooth muscle cell oxidative stress;

(f2) inhibiting vascular smooth muscle cell inflammatory responses;

(f3) inhibiting abdominal aortic oxidative stress;

(f4) inhibiting an abdominal aorta inflammatory response;

(f5) inhibiting vascular smooth muscle cell oxidative stress in patients with abdominal aortic aneurysm;

(f6) inhibiting vascular smooth muscle cell inflammatory response of patients with abdominal aortic aneurysm;

(f7) inhibiting abdominal aortic oxidative stress in patients with abdominal aortic aneurysm;

(f8) inhibiting the inflammation reaction of abdominal aorta of patients with abdominal aortic aneurysm.

The invention also protects a product, the active ingredient of which is cycloastragenol; the product has at least one of the following uses (g1) - (g 4):

(g1) promoting the synthesis of vascular smooth muscle cell elastin;

(g2) promoting the synthesis of abdominal aorta elastin;

(g3) promoting the synthesis of vascular smooth muscle cell elastin of patients with abdominal aortic aneurysm;

(g4) promote the synthesis of the abdominal aorta elastin of patients with abdominal aortic aneurysm.

Any of the above products may be specifically a medicament, a food or a health product.

The invention also provides a medicament for preventing abdominal aortic aneurysm, which comprises the active ingredient of cycloastragenol.

The invention also provides a medicament for treating abdominal aortic aneurysm, which comprises the active ingredient of cycloastragenol.

Any of the above drugs can be introduced into the body such as muscle, intradermal, subcutaneous, intravenous, mucosal tissue by injection, spray, nasal drop, eye drop, osmotic, absorption, physical or chemical mediated method. Or can be mixed with other materials or coated with other materials and introduced into body. If necessary, one or more pharmaceutically acceptable carriers can be added into any one of the medicines. The carrier includes diluent, excipient, filler, binder, wetting agent, disintegrating agent, absorption enhancer, surfactant, adsorption carrier, lubricant, etc. which are conventional in the pharmaceutical field. Any of the above drugs can be made into various forms such as injection, suspension, powder, tablet, granule, etc. The medicaments in various dosage forms can be prepared according to the conventional method in the pharmaceutical field.

The invention provides an application of cycloastragenol in preparation of a medicine for inhibiting abdominal aortic aneurysm, which is clinically related to an abdominal aortic aneurysm disease model, namely a C57BL/6J mouse abdominal aortic aneurysm induced by incubation of abdominal aorta with elastase (2U) is used for carrying out experiments, experiments prove that the occurrence and development of the mouse abdominal aortic aneurysm induced by elastase can be obviously inhibited by oral gavage of the cycloastragenol, and the in-vitro abdominal aortic aneurysm microenvironment cell model can be used for inhibiting the abdominal aortic aneurysm, namely, the cell damage caused by incubation of rat vascular smooth muscle cells with 100ng/mL tumor necrosis factor- α, and the occurrence and development of the abdominal aortic aneurysm can be obviously inhibited by incubation of the cycloastragenol.

The medicine for inhibiting the abdominal aortic aneurysm is safe, low in toxicity and strong in pharmacological action; the raw materials are wide in source and low in price, and can be obtained by hydrolyzing astragalus extract astragaloside IV; the preparation cost is low, the process is simple, and the yield is high; and has definite curative effect. The invention provides a new medicine source for preventing, diagnosing, detecting, protecting, treating and researching the abdominal aortic aneurysm diseases, is easy to popularize and apply, and can generate great social benefits and economic benefits in a short time.

Drawings

FIG. 1 shows the results of the gavage animal experiments with cycloastragenol in example 1.

FIG. 2 shows the results of the gavage animal experiments with cycloastragenol in example 2.

FIG. 3 shows the expression of HO-1 gene, NOX-4 gene, Fibulin-5 gene and MCP-1 gene in example 3.

Detailed Description

The following examples are given to facilitate a better understanding of the invention, but do not limit the invention. The experimental procedures in the following examples are conventional unless otherwise specified. The test materials used in the following examples were purchased from a conventional biochemical reagent store unless otherwise specified. The quantitative tests in the following examples, all set up three replicates and the results averaged.

C57BL/6J mice: sbeft (beijing) biotechnology limited.

SD rat: department of medicine, Beijing university, Experimental department of animal sciences.

Elastase: Sigma-Aldrich, Cat. No. E1250.

Cycloastragenol: chengdu Jintai and pharmaceutical chemistry technologies, Inc., lot number: 160618, respectively; the molecular formula of cycloastragenol is C₃₀H₅₀O₅CAS number: 78574-94-4, the structural formula is as follows:

example 1 use of Cycloastragenol for prevention of Abdominal aortic aneurysm

First, elastase incubation mouse infrarenal aorta induced abdominal aortic aneurysm model

Experimental animals: male C57BL/6J mice (average body weight 23g) at 10 weeks of age.

The experimental animals were divided into model group and sham operation group (12 model groups, 3 sham operation groups).

1. The experimental animals were anesthetized by intraperitoneal injection of 5% chloral hydrate (injected according to body weight, 8. mu.L/g).

2. After the anesthesia in step 1, the infrarenal abdominal aorta is isolated, a section of the abdominal aorta (about 1cm long) with no branches on the anterior wall and the side wall is taken out under the renal artery plane, and the threading mark is fixed. In the model group, gauze soaked with 2U elastase was wrapped around the exposed abdominal aorta, gauze and silk thread were taken out 50min later, and skin was sutured closed. The sham operation group wrapped the periphery of the exposed abdominal aorta with gauze soaked with normal saline, taken out gauze and silk thread after 50min, and closed the abdomen and sutured the skin.

Second, cycloastragenol for intragastric administration

1. After the first step is completed, the mice in the model group are randomly divided into a normal saline group and a cycloastragenol group (6 mice in each group), the mice in the cycloastragenol group are subjected to intragastric perfusion by adopting cycloastragenol every day (the cycloastragenol is dissolved in 0.01M PBS solution, the intragastric perfusion dose is 50mg of cycloastragenol/kg of body weight), the mice in the normal saline group are subjected to intragastric perfusion by adopting normal saline every day (200 mu L/mouse), and the mice in the sham operation group are subjected to intragastric perfusion by adopting normal saline every day (200 mu L/mouse) for 14 days.

2. After completion of step 1, each group of mice was subjected to cardiopulmonary instillation with 0.01M PBS buffer to remove circulating blood, then abdominal aorta tissue was taken for fixed dehydration, fat and connective tissue around the fixedly dehydrated infrarenal abdominal aorta were peeled off under a scope, the heart was cut off, photographing was performed under a black background, the maximum diameter of the infrarenal abdominal aorta was measured, the incidence of abdominal aortic aneurysm of the mice was counted, infrarenal abdominal aorta was taken to make HE-stained paraffin sections and aldehyde magenta-stained paraffin sections.

The results of the photograph of the infrarenal abdominal aorta are shown in FIG. 1A. The largest diameter of the infrarenal abdominal aorta is shown in FIG. 1B. The statistics of the incidence of abdominal aortic aneurysm are shown in fig. 1C (the abdominal aortic aneurysm is considered to occur in mice with a maximum diameter of the abdominal aorta larger than 50% of the normal maximum diameter). HE staining observations are shown in figure 1D. The results of the aldehydic magenta staining are shown in FIG. 1E.

The result shows that compared with the mice in the sham operation group, the blood vessels at the infrarenal part of the mice in the normal saline group have obvious expansion and obvious artery dilation, and the periploysolene can reduce the incidence and degree of the artery dilation. Compared with a sham-operated group of mice, the diameter of the blood vessel under the kidney of the mice can be obviously increased by incubating the elastase, but the vasodilatation caused by incubating the elastase can be obviously reduced by infusing the gastric ring astragaloside every day. Compared with mice in a sham operation group, incubation of elastase obviously increases infiltration of infrarenal artery inflammatory cells, thickening of adventitia and fracture of an elastic plate of the mice, and peridol can inhibit the pathological changes.

Example 2 Cycloastragenol gastric lavage treatment Elastase incubation C57BL/6J mice infrarenal artery induced abdominal aortic aneurysm

The same procedure as in example 1.

Second, cycloastragenol for intragastric administration

1. After 14 days of the first step, the mice in the model group are randomly divided into a normal saline group and a cycloastragenol group (6 mice in each group), the mice in the cycloastragenol group are intragastrically injected with cycloastragenol every day (the cycloastragenol is dissolved in 0.01M PBS solution, the intragastrically injected dose is 125mg of cycloastragenol/kg of body weight), the mice in the normal saline group are intragastrically injected with normal saline every day (200 mu L/mouse), and the mice in the sham operation group are intragastrically injected with normal saline every day (200 mu L/mouse) for 28 days.

2. After the step 1 is completed, perfusing and washing each group of mice by using 0.01M PBS buffer solution, taking abdominal aorta tissue for fixed dehydration, peeling fat and connective tissue around the fixed and dehydrated infrarenal abdominal aorta under a stereoscope, cutting off the heart, taking a picture under a black background, measuring the maximum diameter of the infrarenal abdominal aorta, taking the infrarenal abdominal aorta to prepare an HE stained paraffin section and an aldehyde fuchsin stained paraffin section.

The results of the photograph of the infrarenal abdominal aorta are shown in FIG. 2A. The largest diameter of the infrarenal abdominal aorta is shown in FIG. 2B. The statistics of the incidence of abdominal aortic aneurysm are shown in fig. 2C (mouse abdominal aorta with maximum diameter greater than 50% of normal maximum diameter is considered to have abdominal aortic aneurysm). HE staining observations are shown in figure 2D. The results of the aldehydic magenta staining are shown in FIG. 2E.

The result shows that compared with the mice in the sham operation group, the blood vessels at the infrarenal part of the mice in the normal saline group have obvious expansion and obvious artery dilation, and the periploysolene can reduce the incidence and degree of the artery dilation. Compared with a sham-operated group of mice, the diameter of the blood vessel under the kidney of the mice can be obviously increased by the incubation of the elastase, but the vasodilatation caused by the incubation of the elastase can be obviously reduced by the gavage cycloastragenol. Compared with mice in a sham operation group, incubation of elastase obviously increases infiltration of infrarenal artery inflammatory cells, thickening of adventitia and fracture of an elastic plate of the mice, and peridol can inhibit the pathological changes.

Example 3 inhibition of TNF- α -induced vascular smooth muscle cell injury in rats by Cycloastragenol

Preparation of rat vascular smooth muscle cells

SD rats (body weight about 100g) were anesthetized with 10% chloral hydrate and soaked in 75% alcohol for 2min for sterilization. The thoracic and abdominal cavities are opened, the organs are pushed aside to expose the heart and aorta, and blood is aspirated away with gauze. Carefully cut the heart and aorta to full length until the abdominal aorta bifurcation and immediately place them in 0.01M PBS buffer. Adipose tissue and connective tissue were separated and the heart was carefully trimmed off with three washes of 0.01M PBS buffer. The separated clear aorta was washed once in DMEM containing 0.05g/100ml amphotericin B. The aorta is then cut longitudinally, the intima is scraped off, and the aorta is trimmed. The excised aortic tissue blocks were transferred with forceps to a 3.5cm petri dish plated with 0.1% gelatin, added with 1mL of MEM medium (containing 20% FBS, 100U/mL penicillin and 100. mu.g/mL streptomycin), incubated at 37 ℃ in an incubator, and subcultured. Cells were cultured until 4-6 for the experiment.

2. The smooth muscle cells prepared in step 1 were seeded in 6-well plates (1.5X 10 per well)⁵Individual cells), DMEM medium (containing 10% FBS, 100U/mL penicillin and 100. mu.g/mL streptomycin), 37 ℃ and 5% CO₂Culturing in an incubator until the growth reaches 80 percent.

3. After completion of step 2, the 6-well plate was replaced with DMEM medium (containing 5% FBS, 100U/mL penicillin and 100. mu.g/mL streptomycin), cultured for 12 hours, and subjected to the following grouping treatment:

control group: and culturing for 24 h.

TNF- α group 100ng/mL TNF- α was added per well and incubated for 24 h.

TNF- α + cycloastragenol group, 100ng/mL TNF- α and 31.25 μ g/mL cycloastragenol were added per well and cultured for 24 h.

4. After completion of step 3, each set of cells was collected, total RNA was extracted and reverse transcribed into eDNA. And (3) detecting the expression conditions of the HO-1 gene, the NOX-4 gene, the Fibulin-5 gene and the MCP-1 gene by taking the eDNA as a template. The GAPDH gene was used as a reference gene.

The primer sequences for detecting the HO-1 gene are as follows:

HO-1-F：5’-ACAGAAGAGGCTAAGACCG-3’；

HO-1-R：5’-CAGGCATCTCCTTCCATT-3’。

the primer sequences for detecting the NOX-4 gene are as follows:

NOX-4-F：5’-CCAGATGTTGGGCCTAGGATT-3’；

NOX-4-R：5’-ACTGATACAGCCAGGAGGGT-3’。

the primer sequences for the Fibulin-5 gene are as follows:

Fibulin-5-F：5’-GTTAAGCGAAACCAGGTGCC-3’；

Fibulin-5-R：5’-TCGTCCACATCCACACACTG-3’。

the primer sequences for detecting the MCP-1 gene are as follows:

MCP-1-F：5’-AATGAGTCGGCTGGAGAA-3’；

MCP-1-R：5’-GTGCTTGAGGTGGTTGTG-3’。

the primer sequences for detecting the GAPDH gene were as follows:

GAPDH-F：5’-TGATGACATCAAGAAGGTGGTGAAG-3’；

GAPDH-R：5’-TCCTTGGAGGCCATGTAGGCCAT-3’。

the results are shown in figure 3, and show that TNF- α after incubation for 24h results in a significant decrease in HO-1mRNA expression level, a significant increase in NADPH Oxidase (NOX) -4mRNA level and cell oxidative stress, a significant decrease in Fibulin-5mRNA expression level and influence on elastin synthesis, a significant increase in Monocyte Chemotactic Protein (MCP) -1mRNA expression level and promotion of cell inflammatory response, compared with the control group, and incubation of cycloastragenol can significantly inhibit the change of the above cytokines caused by TNF- α, reduce the cellular oxidative stress and inflammatory response and promote elastin synthesis.

Claims

1. Use of cycloastragenol for the preparation of a medicament for the prevention and/or treatment of abdominal aortic aneurysm.

2. The use according to claim 1, being at least one of (b1) - (b3) as follows:

(b1) preparing a medicament for inhibiting the rupture of an abdominal aorta elastic plate;

(b2) preparing a medicament for inhibiting the thickening of the adventitia of the abdominal aorta;

(b3) preparing the medicine for inhibiting the abdominal aorta vessel dilation.

3. The use according to claim 1, being at least one of (c1) - (c4) as follows:

(c1) preparing a medicament for inhibiting oxidative stress of vascular smooth muscle cells;

(c2) preparing a medicament for inhibiting vascular smooth muscle cell inflammatory response;

(c3) preparing a medicament for inhibiting oxidative stress in the abdominal aorta;

(c4) preparing the medicine for inhibiting the abdominal aorta inflammatory reaction.

4. The use according to claim 1, as follows (d1) or (d 2):

(d1) preparing a medicament for promoting synthesis of vascular smooth muscle cell elastin;

(d2) preparing a medicament for promoting the synthesis of the abdominal aorta elastin.