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Application of tetratype collagen serving as target spot in early-diagnosis of aortic aneurysm/interlayer

A technology for aortic dissection and early diagnosis, applied in the field of diagnosis and treatment of vascular diseases, can solve problems such as high rupture risk and easy torn dissection

Pending Publication Date: 2017-07-28
BEIJING INST OF HEART LUNG & BLOOD VESSEL DISEASES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In recent years, research on big epidemiological data has found that the clinical symptoms of aortic aneurysm are hidden in the very early stage, and the lumen does not appear to expand significantly; A sudden increase in blood pressure is prone to tearing and dissection, and epidemiological data have also confirmed that there is no linear relationship between the diameter of the lumen and the risk of rupture, and some aneurysms with smaller diameters have a higher risk of rupture

Method used

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  • Application of tetratype collagen serving as target spot in early-diagnosis of aortic aneurysm/interlayer
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  • Application of tetratype collagen serving as target spot in early-diagnosis of aortic aneurysm/interlayer

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Embodiment 1, the construction of thoracic aortic dissection / aortic aneurysm mouse model (mouse TAD model)

[0038] Construction and evaluation of TAD model in BAPN water-fed mice

[0039] 3-week-old C57BL / 6 background male mice were given normal diet,

[0040] BAPN water-fed group (n=16): BAPN was dissolved in drinking water at a dose of 1 g / kg / day.

[0041] On the 14th day of feeding BAPN, 5 mice were randomly selected for thoracic aortic ultrasound to determine whether there was widening / dissection of the thoracic aorta. After repeated experiments, some mice had formed aortic dissection / aortic aneurysm at 14 days, and began to die one after another.

Embodiment 2

[0042] Embodiment 2, mouse TAD model tissue section detection

[0043] 1. Frozen section:

[0044] At the end of the experiment, the mice were anesthetized with pentobarbital (100 mg / kg), and the heart was perfused with heparinized saline to remove residual blood in the heart. Perfusion was continued with 4% paraformaldehyde to fix the vascular tissue morphology in situ. The arch and descending part of the aorta were separated and clipped under a stereo microscope, soaked and fixed in 4% paraformaldehyde for 2 hours, and then transferred to 30% sucrose solution at 4°C overnight to fully dehydrate. The blood vessel was taken out from the sucrose solution the next day, and the tissue moisture was fully blotted with filter paper, and the blood vessel was vertically embedded in OCT embedding medium, wrapped in tin foil and slowly frozen in liquid nitrogen, which could be stored at -80°C refrigerator. Serial frozen tissue sections, 5 μm in thickness, were mounted on polylysine-c...

Embodiment 3

[0047] Embodiment 3, mouse TAD model histopathological detection:

[0048] I. Observe the condition of the elastic board through elastic fiber dyeing,

[0049] The specific operation is as follows:

[0050] 1.1. Frozen section:

[0051] (1) Wash off OCT in frozen section PBS;

[0052] (2) Add 1 drop (100 μl) of Lugol's iodine solution (reagent A) and incubate for 5 minutes, then wash with water;

[0053] (3) Add 1 drop (100 μl) of sodium thiosulfate (reagent B) for 5 minutes;

[0054] (4) Rinse with running water for 5 minutes, and wash with 70% alcohol;

[0055] (5) Add 1 drop (100 μl) of aldehyde fuchsin staining solution (reagent C), stain for 10 minutes, soak twice with 70% alcohol (about 30 seconds each time, until the section is no longer decolorized), and wash slightly with water;

[0056] (6) Add 1 drop (100 μl) of Orange G dyeing solution (reagent D) for 10 seconds and wash with water;

[0057] (7) 95% alcohol dehydration for 5 minutes;

[0058] (8) Dehydration...

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Abstract

The invention relates to tetratype collagen serving as a specific molecular target spot in targeted diagnosis and / or treatment aortic interlayer / aneurysm. A COLIV targeted peptide fragment and a derivative thereof are synthesized autonomously, and occurrence of aortic aneurysm / interlayer is monitored at an early stage by monitoring activation of endothelial cells. The monitoring mode refers to one or multiple of ultrasonic detection, MRI detection, CTA detection and fluorescent imaging detection. In addition, the COLIV targeted peptide fragment can serve as a molecule target spot of a targeted drug delivery system, and higher blood drug concentration and less toxic and side effect at a disease position are guaranteed. Drug is drug for administration through gastrointestinal tract, drug for administration through intravenous injection and drug for administration through subcutaneous embedment, and the drug for administration through subcutaneous embedment preferably.

Description

technical field [0001] The present invention relates to the field of diagnosis and treatment of vascular diseases, in particular to a new aortic aneurysm targeting molecule and methods and reagents for early diagnosis and targeted treatment of thoracic aortic aneurysm dissection and abdominal aortic aneurysm. Background technique [0002] Aortic aneurysm (aortic aneurysm) refers to the local or diffuse abnormal expansion of the aortic wall exceeding 50% of the normal diameter. Once it occurs, the rupture rate is as high as 80%. Aortic aneurysms are more likely to occur in large arteries, including the ascending aorta, aortic arch, descending thoracic aorta, thoracoabdominal aorta, and abdominal aorta. Due to the high blood pressure and excessive flow velocity of the aorta, it is very easy to expand rapidly under stress, and even tear to form a dissection, threatening the life of the patient. The traditional diagnosis of aortic aneurysm relies on the combination of imaging ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/06A61K31/352A61K47/64A61P35/00
CPCA61K31/352C07K7/06
Inventor 杜杰徐福建李玉琳徐恪许晨
Owner BEIJING INST OF HEART LUNG & BLOOD VESSEL DISEASES
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