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Tetranectin mimetic peptide tnp and its application

A technology that mimics peptides and linkins, applied in the field of biomedicine, can solve the problems that the role has not been reported, and the function and mechanism of TN are not clear.

Active Publication Date: 2021-06-15
HENAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

TN exists in a variety of tissues and cells, and has been reported to be associated with a variety of diseases, such as tumors, peripheral non-tumor diseases, central nervous system diseases, etc. However, so far, the function and mechanism of TN are unclear, especially Its role in the pathological process of sepsis or acute kidney injury has not been reported

Method used

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  • Tetranectin mimetic peptide tnp and its application
  • Tetranectin mimetic peptide tnp and its application
  • Tetranectin mimetic peptide tnp and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1 Correlation between tetranectin TN and the pathological process of sepsis or acute kidney injury

[0033] Normal subjects (10 cases), pneumonia patients (27 cases), sepsis patients (37 cases), and renal failure patients (17 cases) were selected for the experiment, and western blotting (western blotting, Li W et al. (2018) ) Connexin 43hemichannel as a novel mediator of sterile and infectious inflammatory diseases. Scientific Reports 8(1): 166) Detect the level of TN in the plasma, separate 0.25μL plasma protein, and the plasma protein in the polyacrylamide gel with a mass concentration of 12% After electrophoresis separation and transfer to cellulose acetate membrane, the results of the TN protein band displayed by anti-TN antibody are as follows: figure 1 as shown, figure 1 The middle left bar chart (i.e. figure 1 The shades of the band colors in A1, A2, and B) reflect the difference in the amount of protein, and the gray value represents the relative amoun...

Embodiment 2

[0035] Example 2 Tetranectin mimetic peptide TNP inhibits the release of inflammatory factor HMGB1 from vascular endothelial cells

[0036] The specific composition of the culture medium for human umbilical cord vascular endothelial cells is Dulbecco's Modified Eagle's Medium, namely DMEM, which contains 20% fetal bovine serum, 100 units / ml of penicillin and 100 micrograms / ml of streptomycin. After washing with DMEM without serum and antibiotics, the cells were divided into control group (Cont, without adding any components), TNP group (containing 20 μg / ml TNP), LPS group (containing 1 μg / ml bacterial endotoxin LPS ) and the TNP+LPS group (containing 20 μg / ml of TNP and 1 μg / ml of LPS. After 20 hours, the culture media were collected and concentrated, and then immunoblotting was used to show HMGB1 in them, as figure 2 As shown (sample number n=4, p figure 2 Down).

[0037] Depend on figure 2 It can be seen that the cell culture medium without TNP or LPS (i.e. Cont) contain...

Embodiment 3

[0038] Example 3 Acetylation of tetranectin mimetic peptide TNP can effectively prevent TNP hydrolysis

[0039] In this experiment, 8 Balb / c male mice (body weight about 25 g) at 8 weeks after birth were used. After the mice were intraperitoneally injected with TNP (8 mg / kg body weight), the mice were sacrificed at 15 minutes, 30 minutes, 1 hour and 2 hours respectively, and the blood was collected, and the plasma was extracted by centrifugation and separated by electrophoresis. Then TNP in plasma was detected by the combination of horseradish peroxidase-coupled streptavidin (streptavidin-HRP) and biotin (biotin) in TNP, the results were as follows image 3 shown.

[0040] Depend on image 3 It can be seen that 15 minutes after the injection of TNP, the TNP level in the mouse plasma is the highest, indicating that after intraperitoneal injection, TNP can be quickly absorbed into the circulation system, and then gradually decreased over time, but it can still be detected 2 ho...

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Abstract

The invention relates to the technical field of biomedicine, in particular to tetranectin-mimicking peptide TNP and its application in treating diseases caused by the release of HMGB1 from vascular endothelial cells. The sequence of the acetylated tetranectin mimetic peptide at the nitrogen end is Ac‑QPDGGKTENCAVLSGAANGKWFDKRCRDK‑biotin. The acetylated tetranectin mimetic peptide TNP can effectively prevent the hydrolysis of TNP and prolong its half-life to improve the biological efficacy of the drug. TNP is in use When preparing drugs for the treatment of sepsis and other diseases, it can effectively inhibit the release of HMGB1 from vascular endothelial cells, reduce the concentration of extracellular HMGB1, and reduce the death rate of septic mice, and can almost completely block renal ischemia-reperfusion in mice. Changes in plasma urea nitrogen and creatinine can reduce renal tubular necrosis after ischemia, achieve the purpose of treating acute kidney injury, and provide a new way for the diagnosis and treatment of human diseases caused by the release of HMGB1 from vascular endothelial cells.

Description

technical field [0001] The invention relates to the technical field of biomedicine, and relates to a tetranectin-mimetic peptide TNP and its application, in particular to a tetranectin-mimetic peptide TNP and its application in the preparation of medicines for treating diseases caused by the release of HMGB1 from vascular endothelial cells. Background technique [0002] Sepsis is multiorgan failure caused by an infection-triggered host response. There are about 30 million patients in the world every year, and the case fatality rate reaches 20-70%. Therefore, it was identified as a major threat to human health by the World Health Assembly in 2017. [0003] Acute kidney injury (acute kidney injury, AKI) refers to the creatinine level in the patient's serum increases to 0.3 mg / 100 ml within 48 hours or increases by 50% within 7 days. AKI is a common disease in hospitalized patients, especially in intensive care units, with a mortality rate of about 18.9-46.5%. AKI has infect...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/00C07K1/107A61K38/16A61P9/10A61P1/16A61P13/12A61P9/14A61P11/00A61P31/04
CPCA61K38/00A61P1/16A61P9/10A61P9/14A61P11/00A61P13/12A61P31/04C07K14/00
Inventor 李伟王帅伟张祎捷
Owner HENAN UNIVERSITY
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