Pharmaceutical application of asparagine endopeptidase inhibitor

A technology of asparagine and endopeptidase, applied in the field of medicine

Active Publication Date: 2021-06-25
ZHONGSHAN HOSPITAL FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the role of Lgmn in the phenotypic transformation of aortic smooth muscle and the occurrence of aortic dissection has not been reported yet.

Method used

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  • Pharmaceutical application of asparagine endopeptidase inhibitor
  • Pharmaceutical application of asparagine endopeptidase inhibitor
  • Pharmaceutical application of asparagine endopeptidase inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1: Detection of Human Aortic Vascular Tissue

[0025] Immunofluorescence staining was carried out on healthy human aortic vascular tissue (Health group) and aortic dissection vascular tissue (TAD group), and the experimental results showed that the expression of Lgmn in the TAD group was significantly increased, see figure 1 Middle A, B.

Embodiment 2

[0026] Example 2: The expression of Lgmn is significantly increased in the aortic dissection model

[0027] Take C57BL / 6 mice, 20 in each group, and divide them into a control group (healthy mice without modeling, Sham) and a TAD model group. The control group is fed with purified water, and the TAD model group is fed with 0.5% BAPN drinking water. All mice were given normal diet, and after 4 weeks of feeding, the aortic dissection model was successfully established, and then the expression of Lgmn in the aortic dissection vessels of the control group and the TAD model group was detected. Through Western blot and real-time fluorescent quantitative PCR experiments, we found that compared with the control group, the TAD model group showed significantly increased Lgmn expression. In addition, the Lgmn content in the mouse serum was detected by ELISA method, and we found that compared with the control group, the Lgmn level in the serum of the mice in the TAD model group increased ...

Embodiment 3

[0028] Example 3: Lgmn knockout improves the occurrence of BAPN-induced aortic dissection

[0029] Take C57BL / 6 mice, 20 in each group, and divide them into Lgmn knockout group (Lgmn - / - ) and TAD model group (WT), were fed with 0.5% BAPN drinking water for 4 weeks to establish the aortic dissection model, and then the survival curve of the mice and the occurrence of dissection were calculated. Vascular ultrasound detection of aortic vessel diameter. The results are reflected in image 3 Middle, A: The general morphology of blood vessels in the Lgmn knockout group and the TAD model group; B: The survival curve statistics of the Lgmn knockout group and the TAD model group; C: The statistics of the incidence of aortic dissection in the Lgmn knockout group and the TAD model group; D and E represent the changes in vessel diameter detected by ultrasound in the Lgmn knockout group and the TAD model group; F: HE and EVG staining, and the morphological changes of the blood vessels i...

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Abstract

The invention requests to protect the application of the asparagine endopeptidase inhibitor RR-11aanalog in preparation of the medicine for treating the aortic dissection, it is found through experiments that asparagine endopeptidase serves as a target spot for occurrence of the aortic dissection, and the RR-11aanalog has the effect of treating the aortic dissection and has great clinical significance in further development of related treatment medicine.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a pharmaceutical application of an asparagine endopeptidase inhibitor. Background technique [0002] Aortic dissection (TAD) refers to structural abnormalities such as degeneration, degeneration, and necrosis of the aortic media under the influence of various predisposing factors such as hypertension, atherosclerosis, and genetic defects. On the upper side, the intima is torn, and blood enters the middle layer to form a false lumen, or the intramural hematoma forms a false lumen due to the rupture of the nutrient vessel in the arterial wall, and the false lumen gradually expands and develops into a dissection. Aortic dissection is a highly fatal disease in which rupture of the aorta can lead to sudden death. At present, the specific pathogenesis of non-hereditary TAD has not yet been elucidated, and there is no effective prevention and drug treatment for TAD. Therefore, the re...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/08A61P9/00A61P9/14
CPCA61K38/08A61P9/00A61P9/14
Inventor 孙爱军葛均波潘丽虹柏佩原
Owner ZHONGSHAN HOSPITAL FUDAN UNIV
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