TNF (Tumor Necrosis Factor) receptor associated factor 1 (TARF1) and application of inhibitor thereof to liver ischemic disease

A technology of liver ischemia and inhibitor, applied in cardiovascular system diseases, antibodies, gene therapy, etc.

Active Publication Date: 2014-05-14
WUHAN UNIV
View PDF1 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although other TRAF family members are widely distributed in different tissue cells, TRAF1 mRNA can only be detected in a few tissues such as spleen, lung, and testis

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • TNF (Tumor Necrosis Factor) receptor associated factor 1 (TARF1) and application of inhibitor thereof to liver ischemic disease
  • TNF (Tumor Necrosis Factor) receptor associated factor 1 (TARF1) and application of inhibitor thereof to liver ischemic disease
  • TNF (Tumor Necrosis Factor) receptor associated factor 1 (TARF1) and application of inhibitor thereof to liver ischemic disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042][Example 1] Construction of hepatocyte-specific TRAF1 transgenic mice

[0043] To further study the effect of TRAF1 overexpression on liver ischemia / reperfusion injury, we constructed several strains of hepatocyte-specific TRAF1 transgenic mice (TRAF1-TG). Transgenic vector construction information: use TRAF1 gene upstream primer, namely 5'-GAACTCGAGCCACCATGGCCTCCAGCTCAGCCCC-3' (SEQ ID NO. 1); TRAF1 gene downstream primer, namely 5'-GAATGCGGCCGCCTAAGCACTAGTGTCCACAA-3' (SEQ ID NO. 2), amplify Mouse TRAF1 full-length gene (NCBI, Gene ID: 22029, XM_006497845.1), insert the cDNA into the pGEM-T vector (Promega company product, product number A1360) downstream of the Albumin promoter, and construct the vector into fertilization by microinjection embryos (C57BL / 6 background), and hepatocyte-specific TRAF1 transgenic mice were obtained. Genomic DNA was obtained from the transgenic mice by cutting their tails, and PCR was used to identify and detect the structure of the exogeno...

Embodiment 2

[0047] [Example 2] A mouse liver ischemia-reperfusion injury model (ischemia / reperfusion injury, I / R) was obtained

[0048] 1. Grouping of experimental animals: male C57BL / 6 strain wild-type mice, TRAF1 knockout mice, TRAF1 transgenic mice and non-transgenic mice. Liver ischemia model was established by liver ischemia-reperfusion (I / R). They were randomly divided into 8 groups: C57BL / 6J strain wild type mice sham operation group (WT SHAM) and I / R operation group (WT I / R), TRAF1 gene knockout mouse sham operation group (KO SHAM) and I / R operation group R operation group (KO I / R), non-transgenic mouse sham operation group (NTG SHAM) and I / R operation group (NTG I / R), liver cell-specific TRAF1 transgenic mouse sham operation group (TG SHAM) and I / R surgery group (TG I / R).

[0049] 2. I / R operation of the liver ischemia-reperfusion injury model (the portal vein and hepatic artery in the middle lobe and left lobe are clamped with non-invasive vascular clips, so that about 70% of t...

Embodiment 3

[0056] [Example 3] Determination of liver necrosis area and liver function index

[0057] The evaluation indicators of the severity of liver ischemia / reperfusion injury mainly include the area of ​​liver necrosis and liver function indicators (AST, ALT), all of which are positively correlated with the severity of liver ischemia / reperfusion injury.

[0058] 1. Take materials

[0059] Mice were killed by cervical dislocation in the sham operation group (Sham) and at 12h, 24h, and 48h after ischemia-reperfusion, and 1 mL of blood was collected from the inferior vena cava immediately to separate the serum. At the same time, the left lobe of the liver in the ischemic area with a size of about 1.5cm×1cm×0.2cm was fixed in 10% neutral formalin for 24 hours, dehydrated, embedded, paraffin-sectioned, and then stained with HE. (Separation of serum: the EP tube that collects the blood is left at room temperature for 1-2 hours to allow the blood to coagulate naturally. Centrifuge at 4°C ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention discloses application of an inhibitor of TRAF1 (TNF Receptor Associated Factor 1) to liver ischemic disease, belonging to the field of biomedicines. A TRAF1 gene knock-out mouse and a hepatocyte specific TRAF1 transgenic mouse are taken as experimental objects, and a hepatic ischemia reperfusion injury model is adopted. As proved by a result, the hepatic necrosis of the TRAF1 gene knock-out mouse is inhibited remarkably and the liver function is improved remarkably in comparison to those of a wild C57 mouse while the hepatic necrosis of the hepatocyte specific TRAF1 transgenic mouse is increased remarkably and the liver function deteriorates remarkably. Thus, the TRAF1 gene has the effect of deteriorating the liver function, and can particularly deteriorate liver ischemic disease. Aiming at the functions of the TRAF1, application of the TRAF1 as a medicinal target in treatment of liver ischemic disease to the preparation of medicaments for treating liver ischemic disease is provided.

Description

[0001] technical field [0002] The invention belongs to the field of gene function and application, and in particular relates to the application of tumor necrosis factor (TNF) receptor-associated factor 1 (TNF receptor-associated factor 1, TRAF1) as a drug target in screening and treating drugs for liver ischemic diseases , and the application of TRAF1 inhibitors in the preparation of drugs for treating hepatic ischemic diseases. [0003] Background technique [0004] Ischemia / reperfusion injury (I / R) is one of the hot issues in current research. The mechanism is quite complex and many factors are involved. Current theoretical research and clinical practice have confirmed that when the blood supply is blocked for more than 30 minutes, it will cause changes in the ultrastructure and dysfunction of various organelles, resulting in irreversible damage and even death of cells. Timely restoration of blood supply is regarded as saving this part of the tissue. important measure...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K48/00A61K39/395A61P1/16A61P9/10C12Q1/68
Inventor 李红良张晓东张晓飞张艳蒋丁胜刘小熊
Owner WUHAN UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products