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Application of AKT2 inhibitor in preparation of medicine for treating non-alcoholic fatty liver disease

A fatty liver disease, non-alcoholic technology, applied in the application field of AKT2 inhibitors in the preparation of non-alcoholic fatty liver disease treatment drugs

Active Publication Date: 2021-10-19
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no report on the role of AKT2 inhibitors in reducing abnormal fat metabolism in the liver, relieving liver oxidative stress damage, and treating NAFLD.

Method used

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  • Application of AKT2 inhibitor in preparation of medicine for treating non-alcoholic fatty liver disease
  • Application of AKT2 inhibitor in preparation of medicine for treating non-alcoholic fatty liver disease
  • Application of AKT2 inhibitor in preparation of medicine for treating non-alcoholic fatty liver disease

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] 1. Construction of animal models

[0026] All mice were randomly divided into four groups according to genotype: WT, WT-HFD, AKT2 KO and AKT2 KO-HFD, with ten mice in each group, and fed continuously for 12 weeks. Ordinary feed: 20 kcal% protein, 70 kcal% carbohydrate, 10 kcal% fat; high-fat feed: 20 kcal% protein, 35 kcal% carbohydrate, 45 kcal% fat; free access to food and water, weekly rat cage Carry out cleaning and disinfection, and change drinking water regularly. The body weight of the mice was recorded every week, and the food intake was recorded the next day. After the modeling was completed, the liver tissue was weighed and stored at -80°C for testing. The weight of the liver was as follows: figure 1 As shown, there was no significant difference between WT and WT-HFD and between AKT2 KO and AKT2 KO-HFD, indicating that HFD had no effect on the liver weight of mice of the two genotypes.

[0027] 2. Determination of TG and TC content in mouse liver

[0028] ①...

Embodiment 2

[0054] 1. L02 cell culture

[0055] ① Preparation of medium: DMEM medium with 4.5g / L glucose, 10% FBS, 1% penicillin and streptomycin;

[0056] ②Inoculation: Inoculate L02 cells into corresponding well plates and place them in a cell culture incubator at 37°C containing 5% carbon dioxide and 95% air;

[0057] ③Starved cells: After culturing overnight, remove the medium and replace it with 4.5g / L glucose-free DMEM medium without serum, and starve L02 cells for 12h;

[0058] ④Experimental grouping: 1mM free fatty acid (oleic acid:palmitic acid=2:1); divided into blank group, con group (DMEM medium of 1%BSA+4.5g / L glucose+1% penicillin and streptomycin) , the model group, that is, the HFD group ((1mM free fatty acid+1%BSA+4.5g / L glucose DMEM medium+1% penicillin streptomycin), the experimental group, that is, the HFD+AKT2 inhibitor group (1mM free fatty acid+ 1%BSA+10µM AKT2 inhibitor (CCT128930)+4.5g / L glucose in DMEM medium+1% penicillin and streptomycin)

[0059] 2. MTT exp...

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Abstract

The invention discloses an application of an AKT2 inhibitor in the preparation of a medicine for treating a non-alcoholic fatty liver disease, and belongs to the technical field of biological medicines. Pharmacological experiment results prove that the AKT2 inhibitor (CCT128930) has a good treatment effect on an L02 cell lipid deposition model induced by free fatty acid for the first time, lipid deposition in cells and ROS level in cytoplasm are reduced, and Caspase 3 enzyme activity can be reduced, so that cell apoptosis caused by free fatty acid is reduced. The AKT2 inhibitor is used for preparing the medicine for treating the non-alcoholic fatty liver disease, the curative effect is definite, the effect is obvious, the side effect is low, and the medical application prospect is wide.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of an AKT2 inhibitor in the preparation of medicines for treating nonalcoholic fatty liver disease. Background technique [0002] Nonalcoholic fatty liver disease (NAFLD) is a clinical syndrome characterized by excessive fat deposition caused by pathological changes similar to alcoholic hepatitis but without a history of excessive drinking and other definite liver damage factors. Genetic predisposition closely associated with acquired metabolic stress-induced liver injury. Classified according to the degree of pathological changes and whether the diseased liver tissue is accompanied by inflammation and fibrosis, NAFLD is mainly composed of simple fatty liver (SFL), nonalcoholic steatohepatitis (NASH) and related liver cirrhosis. With the globalization of obesity and related metabolic syndrome, non-alcoholic fatty liver disease has become the main ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/519A61P1/16A61P3/06
CPCA61K45/00A61K31/519A61P1/16A61P3/06
Inventor 叶俊梅高舒雅陈佳雯包萌萌
Owner CHINA PHARM UNIV
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