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Application in preparation of medicament for preventing and controlling lipopolysaccharide-induced acute liver damage

A technology for acute liver injury and lipopolysaccharide, which is applied in the field of preparation of drugs for the prevention and treatment of lipopolysaccharide-induced acute liver injury, can solve problems such as PKD that are rarely studied, and achieve broad application fields, significant social and economic significance Effect

Inactive Publication Date: 2010-12-01
THE FIRST AFFILIATED HOSPITAL OF THIRD MILITARY MEDICAL UNIVERSITY OF PLA
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But so far, little research has been done on whether and how PKD is involved in the process of LPS-induced inflammation-driven liver injury

Method used

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  • Application in preparation of medicament for preventing and controlling lipopolysaccharide-induced acute liver damage
  • Application in preparation of medicament for preventing and controlling lipopolysaccharide-induced acute liver damage
  • Application in preparation of medicament for preventing and controlling lipopolysaccharide-induced acute liver damage

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Embodiment Construction

[0025] The following will refer to the accompanying drawings, for PKD inhibitors The role of anti-LPS-induced acute liver injury is described in detail.

[0026] and Purchased from Sigma, USA (No.G1171 and No.G1918); LPS (Escherichia coli, 0111: B4), D-GalN (D-galactosamine) were purchased from Sigma; phosphorylated PKD (Ser744 / 748 and Ser916) Antibody, phosphorylated extracellular signal-regulated kinase (phospho-extracellular signal-regulated kinase, p-ERK), phosphorylated c-Jun N-terminal kinase (phospho-c-Jun N-terminal kinase, p-JNK), phosphorylated p38MAPK (p-p38MAPK) and β-actin antibodies were purchased from Cell Signaling Technology (Boston, MA, USA); intercellular adhesion molecule-1 (Intercellular adhesion molecule-1, ICAM-1), vascular cell adhesion molecule-1 ( vascular cell adhesion molecule-1, VCAM-1), endothelial leukocyte adhesion molecule-1 (endothelial leukocyte adhesion molecule-1, ELAM-1) antibodies were purchased from Abcam (Cambridge, UK); horseradis...

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Abstract

The invention relates to new application of a compound, in particular to application in the preparation of a medicament for preventing and controlling lipopolysaccharide (LPS)-induced acute liver damage. A protein kinase D (PKD) inhibitor has the advantages of preventing LPS-induced mice acute liver damage, remarkably reducing the phosphorylation level of LPS-induced PKD, lowering death rate and levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), improving inflammatory reaction, restraining the signal channel of LPS activated p38 mitogen-activated protein kinase (p38MAPK), lowering the level of LPS-induced tumor necrosis factor-alpha (TNK-alpha), reducing the apoptosis number of hepatic cells, the activation of caspases and the expression level of hepatic tissue adhesion molecules and lowering the activation level of myeloperoxidase (MPO).

Description

technical field [0001] The present invention relates to new applications of compounds, in particular to Application in preparation of medicine for preventing and treating acute liver injury induced by lipopolysaccharide. Background technique [0002] Protein kinase D (Protein kinase D, PKD) is a newly discovered serine / threonine protein kinase with unique structure, enzymatic properties and regulatory properties. PKD can be activated by a variety of stimuli, and the activation mode is related to the phosphorylation of serine 744 / 748 (Ser-744 / 748) and serine 916 (Ser-916) in the activation loop of its catalytic domain. Studies have shown that PKD is involved in various cellular responses such as oxidative stress, signal transduction, gene expression and cell survival. Recent studies have found that PKD plays a key role in the host defense response process. For example, PKD can phosphorylate Toll like receptor 5 (Toll like receptor 5, TLR5) serine 805, this phosphorylation...

Claims

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Application Information

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IPC IPC(8): A61K31/407A61P1/16
Inventor 段光杰刘友生朱江许成燕徐小明
Owner THE FIRST AFFILIATED HOSPITAL OF THIRD MILITARY MEDICAL UNIVERSITY OF PLA
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