Application of heat shock factor 2 binding protein in liver ischemia-reperfusion injury and drug-induced liver injury

A technology for drug-induced liver injury and reperfusion injury, applied in the field of gene function and application, can solve the problems of unclear role of liver disease and little research.

Active Publication Date: 2021-07-02
崇好科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there are not many studies on HSF2BP. Existing studies have shown that the expression of HSF2BP is increased in the brain lesions of patients with multiple sclerosis. It can interact with breast cancer-associated protein 2, participate in the formation of sperm, and may be associated with the occurrence of coronary artery disease. related, but its role in liver disease remains unclear

Method used

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  • Application of heat shock factor 2 binding protein in liver ischemia-reperfusion injury and drug-induced liver injury
  • Application of heat shock factor 2 binding protein in liver ischemia-reperfusion injury and drug-induced liver injury
  • Application of heat shock factor 2 binding protein in liver ischemia-reperfusion injury and drug-induced liver injury

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] [Example 1] Construction of liver cell-specific HSF2BP overexpression and knockout mice:

[0031] To further study the effect of HSF2BP overexpression on liver ischemia-reperfusion injury, we constructed liver-specific HSF2BP overexpression (TG) and knockout (KO) mice. Real-time quantitative PCR (q-PCR) experiments found that the expression of HSF2BP gene in the liver of overexpression mice was significantly increased, while the expression of HSF2BP gene in the liver of knockout mice was significantly decreased (such as figure 1 Middle A, B).

Embodiment 2

[0032] [Example 2] Construction of mouse liver ischemia-reperfusion injury model:

[0033]1. Grouping of experimental animals: male TG, NTG, KO and WT mice aged 8-12 weeks and weighing 20-25g were used as research objects, and divided into 8 groups, namely sham mice with HSF2BP overexpression and non-overexpression mice Operated (NTG-Sham and TG-Sham) and surgical groups (NTG-I / R and TG-I / R); sham-operated (WT-Sham and KO-Sham) of HSF2BP knockout mice and wild-type mice and In the operation group (WT-I / R and KO-I / R), the model of liver ischemia-reperfusion injury was established.

[0034] 2. Operation procedure of liver ischemia-reperfusion injury model:

[0035] 1) The mice were fasted 12 hours before the operation and had free access to water.

[0036] 2) After isoflurane inhalation anesthesia, the patients were fixed in supine position, the abdominal hair was shaved and disinfected.

[0037] 3) Take an incision about 3 cm from the center of the abdomen and enter the abdo...

Embodiment 3

[0040] [Example 3] Construction of a drug-induced liver injury model in mice:

[0041] 1. Grouping of experimental animals: male TG, NTG, KO and WT mice aged 8-12 weeks and weighing 20-25g were used as research objects, and divided into 8 groups, namely sham mice with HSF2BP overexpression and non-overexpression mice Surgery (NTG-Sham and TG-Sham) and model group (NTG-APAP and TG-APAP); sham operation (WT-Sham and KO-Sham) and model group of HSF2BP knockout mice and wild-type mice (WT-APAP and KO-APAP), and then establish a drug-induced liver injury model.

[0042] 2. The operation process of the drug-induced liver injury model:

[0043] 1) The mice were fasted 12 hours before the administration and allowed to drink water freely.

[0044] 2) After the injection site was sterilized, APAP (500 mg / kg) was injected intraperitoneally.

[0045] 3) Collect mouse serum and liver samples 6 hours after administration.

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Abstract

The invention discloses the application of heat shock factor 2 binding protein (HSF2BP) in liver ischemia-reperfusion injury and drug-induced liver injury, and belongs to the field of gene function and application. The present invention takes liver-specific HSF2BP gene overexpression and knockout mice as experimental objects, and through liver ischemia-reperfusion injury and drug-induced liver injury models, the results show that compared with wild-type C57 mice, HSF2BP gene overexpression mice in In the two models, the liver damage was significantly inhibited, and the liver function was significantly improved, while the liver damage in the HSF2BP gene knockout mice was significantly increased, and the liver function was significantly deteriorated in the two models. Therefore, the HSF2BP gene has the function of protecting the liver from damage, especially the protection from ischemia-reperfusion-induced liver damage and drug-induced liver damage. According to the above functions of HSF2BP, its specific agonist can promote the expression of HSF2BP gene to intervene in liver ischemia-reperfusion injury and drug-induced liver injury.

Description

technical field [0001] The invention belongs to the technical field of gene function and application, and particularly relates to the application of HSF2BP (MEILB2) as a drug target in the screening and treatment of drugs for liver ischemia-reperfusion injury and drug-induced liver injury, and the use of HSF2BP agonists in the preparation and treatment of liver ischemia Application of drugs in reperfusion injury and drug-induced liver injury. Background technique [0002] Liver injury caused by ischemia reperfusion (I / R) is an important cause of severe trauma, burns, blood loss, septic shock, and hepatic insufficiency and failure after liver resection and liver transplantation. In recent years, with the increasing clinical popularity of liver resection and liver transplantation, liver I / R injury has become an important bottleneck restricting the development of liver surgery. Liver I / R injury involves a series of complex pathophysiological processes, including intracellular ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): G01N33/68A61K45/00A61P1/16
CPCG01N33/68A61K45/00A61P1/16G01N2800/08
Inventor 吴荣谦张佳毕建斌
Owner 崇好科技有限公司
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