Application of FSTL1 gene or protein in preparation of medicine for preventing and / or intervening abdominal aortic aneurysm

Abstract

The invention belongs to the field of gene protein function research, and particularly relates to application of an FSTL1 gene or protein in preparation of a medicine for preventing and / or intervening abdominal aortic aneurysm. It is found for the first time that the FSTL1 can reduce the occurrence rate of abdominal aortic aneurysm of mice, reduce the maximum diameter of the abdominal aorta of the mice and relieve the elastic fiber fracture degree of the abdominal aorta of the mice, and therefore the FSTL1 has the potential of serving as a medicine for preventing and / or intervening the abdominal aortic aneurysm.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of gene protein function research, and particularly relates to application of FSTL1 gene or protein in preparation of a medicine for preventing and / or intervening abdominal aortic aneurysm. BACKGROUND

[0002] Abdominal aortic aneurysm is a very dangerous aortic disease, which can suddenly rupture when it develops to a certain stage, and once it ruptures, the mortality can be as high as 90%. The only effective method in clinic at present is surgical intervention, i.e. surgical correction or endovascular intervention surgery, but these methods are only suitable for abdominal aortic aneurysm with vascular diameter expansion beyond a certain range (AAA inner diameter of male and female patients is greater than 55 mm and 50 mm respectively), and there is a risk of trauma and complications. Clinical studies have shown that early elective surgery for small diameter abdominal aortic aneurysm patients does not reduce mortality, but rather increases the perioperative risk (Lindeman JH. The pathophysiologic basis of abdominal aortic aneurysm progression: a critical appraisal. Expert Rev Cardiovasc Ther. 2015; 13: 839-51; Powell JT, et al. Final 12-year follow-up of surgery versus surveillance in the UK Small Aneurysm Trial. Br J Surg. 2007; 94: 702-8; Long-term outcomes of immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med. 2002, 346: 1445-52.). Most small diameter abdominal aortic aneurysms will continue to expand, and their risk of rupture will also increase (Mortality results for randomised controlled trial of early elective surgery or ultrasonographic surveillance for small abdominal aortic aneurysms. Lancet. 1998; 352: 1649-55.). However, there is currently no effective drug in clinic that can delay the progression of abdominal aortic aneurysm. SUMMARY

[0003] The application aims to overcome the defects and deficiencies of the prior art, and provide an application of FSTL1 gene or protein in preparing a drug for preventing and / or intervening abdominal aortic aneurysm.

[0004] The application is achieved by the following technical scheme: the application of FSTL1 gene or protein in preparing a drug for preventing and / or intervening abdominal aortic aneurysm is based on the finding that FSTL1 protein can reduce the incidence of abdominal aortic aneurysm in mice, reduce the maximum abdominal aortic diameter of mice, and reduce the elastic fiber rupture degree of abdominal aorta in mice.

[0005] The active ingredient of the drug comprises a recombinant expression vector cloned with FSTL1 gene and / or FSTL1 protein.

[0006] The recombinant expression vector cloned with FSTL1 gene can effectively perform transcription and translation after entering the organism, and overexpress FSTL1 protein in the organism.

[0007] The dosage form of the drug comprises a freeze-dried powder injection and an oral preparation.

[0008] The oral preparation comprises tablets and capsules.

[0009] The application has the following advantages and effects relative to the prior art: FSTL1 is a folliculin-like protein 1, which is a cysteine-rich extracellular matrix glycoprotein. The application first finds that FSTL1 can reduce the incidence of abdominal aortic aneurysm in mice, reduce the maximum abdominal aortic diameter of mice, and reduce the elastic fiber rupture degree of abdominal aorta in mice. Therefore, FSTL1 has the potential to be used as a drug for preventing and / or intervening abdominal aortic aneurysm. BRIEF DESCRIPTION OF DRAWINGS

[0010] Figure 1 is a measurement result graph of the incidence of abdominal aortic aneurysm in mice.

[0011] Figure 2 is a measurement result graph of the maximum abdominal aortic diameter of mice; wherein the left graph is a photo graph, and the right graph is a statistical result graph.

[0012] Figure 3 is a detection result graph of the elastic fiber rupture degree of abdominal aorta in mice; wherein the left graph is a photo graph, and the right graph is a statistical result graph. DETAILED DESCRIPTION

[0013] The application will be further described in detail below in combination with examples and drawings, but the implementation manner of the application is not limited thereto.

[0014] Example 1 1. Experiment (1) Animal experiment Take 20 weeks old APOE- / - male mice (Jiangsu Jiqie Pharmaceutical Biological Technology Co., Ltd.), subcutaneously implanted with a capsule osmotic pump (purchased from Alzet) loaded with angiotensin (Angiotensin) II solution on the back of the mouse, the dose of angiotensin II is 1.44 mg / kg / day. Abdominal injection of PBS (as a control group) or FSTL1 recombinant protein (purchased from PeproTech, 100 μg / kg) was started on the 7th day after operation, every other day injection, continuous injection for 3 weeks, 12 mice in each group of experimental and control groups. After 28 days, the mice were taken. The maximum outer diameter of the abdominal aorta of the mice was measured, and the incidence of abdominal aortic aneurysm (aortic diameter >1.22 mm was defined as abdominal aortic aneurysm) was calculated. The abdominal aortic blood vessels of the mice were taken for OCT embedding, and the vascular tissue lesions were detected.

[0015] (2) Histological staining Take the blood vessels containing the maximum diameter of the abdominal aorta of the mouse, and quickly freeze in OCT at -80 ℃, and cut the cross-section from the proximal to the distal end of the aorta (8 μm per slice), and then stained with hematoxylin and eosin. Then use Elastica van Gieson staining kit (source: leagene) to observe the degree of elastic fiber rupture of abdominal aorta, and use Image J software to quantify the staining results. The scoring criteria are: (1) no elastic fiber rupture; (2) slight rupture (<25%); (3) moderate rupture (25%-50%); (4) moderate to severe rupture (50%-75%); (5) severe rupture (>75%).

[0016] 2、Results The results of the incidence of abdominal aortic aneurysm are shown in Figure 1 It can be seen that the incidence of abdominal aortic aneurysm in the PBS-treated group of mice was 83.3%, while the incidence of abdominal aortic aneurysm in the FSTL1-treated group of mice was 41.7%. It is suggested that the incidence of abdominal aortic aneurysm in the FSTL1-treated group of mice is significantly reduced.

[0017] The results of the measurement of the maximum abdominal aortic diameter are shown in Figure 2 It can be seen that the average maximum abdominal aortic diameter of the PBS-treated group of mice was 1.86 mm, while the average maximum abdominal aortic diameter of the FSTL1-treated group of mice was 1.30 mm, and the maximum abdominal aortic diameter of the FSTL1-treated group of mice was significantly reduced.

[0018] The results of the detection of the degree of elastic fiber rupture of the abdominal aorta of the mice are shown in Figure 3 It can be seen that the degree of elastic fiber rupture of the abdominal aorta of the FSTL1-treated group of mice is significantly reduced.

[0019] The above embodiments are the preferred embodiments of the present application, but the embodiments of the present application are not limited to the above embodiments, and any changes, modifications, substitutions, combinations, simplifications, etc. made without departing from the spirit and principles of the present application should be equivalent replacement manners and should be included in the protection scope of the present application.

Claims

1. Use of FSTL1 gene or protein in the preparation of a medicament for preventing and / or intervening abdominal aortic aneurysm.

2. Use according to claim 1, characterized in that: The active ingredient of the medicament comprises a recombinant expression vector cloned with FSTL1 gene and / or FSTL1 protein.

3. Use according to claim 1, characterized in that: The dosage form of the medicament is a freeze-dried powder injection or an oral preparation.

4. Use according to claim 3, characterized in that: The oral preparation is a tablet or a capsule.

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