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Application of PSMB8 and PSMB8 inhibitor to preparation of medicine for treating fatty liver and related diseases

An inhibitor, fatty liver technology, applied in the field of gene function and application

Active Publication Date: 2018-06-08
武汉惠康达科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, so far, no reports have found the role of PSMB8 and its inhibitors in fatty liver disease

Method used

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  • Application of PSMB8 and PSMB8 inhibitor to preparation of medicine for treating fatty liver and related diseases
  • Application of PSMB8 and PSMB8 inhibitor to preparation of medicine for treating fatty liver and related diseases
  • Application of PSMB8 and PSMB8 inhibitor to preparation of medicine for treating fatty liver and related diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0082] [Example 1] Effect of PSMB8 knockout on lipid accumulation in primary mouse hepatocytes.

[0083] The primary hepatocytes isolated from WT mice and PSMB8-KO mice were divided into three groups, namely WT primary hepatocytes 0h group, WT primary hepatocytes 12h group, WT primary hepatocytes 24h group, KO Primary hepatocyte 0h group, KO primary hepatocyte 12h group, KO primary hepatocyte 24h group. When the cells adhered to the wall and the cell density was about 30%, 0.6 mmol / l palmitic acid and 1.2 mmol / l oleic acid were added to the cells of the 12h group and 24h group for combined stimulation, and the same volume of BSA was added to the 0h group as a control. After the stimulation time was up, the cell samples of each group were collected for Oil Red O staining, and photographed to observe the accumulation of lipid droplets.

[0084] The results of Oil Red O staining were as follows: figure 1 As shown, after stimulation with palmitic acid and oleic acid, the area of...

Embodiment 2

[0085] [Example 2] PR-957 can significantly inhibit the occurrence and development of HFHC-induced fatty liver

[0086] WT mice were divided into two groups, one was the control group and the other was the PR-957 administration group. After the two groups of mice were fed with HFHC diet for 6W, the PR-957 administration group was injected with PR-957 intraperitoneally for 6W, 3 times a week (Monday, Wednesday, Friday); the control group was injected with the same amount at the same time point. amount of solvent, and HFHC diet was also given during the injection. Before the injection and after the 6W administration, the fasting body weights of the mice in the two groups were weighed; after the administration, the materials were collected, white fat was taken and weighed, and the liver tissues were taken for PAS, HE, Oil Red O and PSR staining. To evaluate the effect of PR-957 on HFHC-induced fat accumulation and hepatic steatosis.

[0087] The weight test results are as follo...

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Abstract

The invention discloses application of PSMB8 and a PSMB8 inhibitor to preparation of medicine for treating fatty liver and related diseases. Primary hepatocytes of C57BL / 6 wild type mice and PSMB8 knock-down C57BL / 6 mice are separated; the functions of PSMB8 gene are studied by a palmitate and oleic acid stimulation induced liver cell lipid accumulation model. The result proves that when the PSMB8expression is lowered, the PA+OA stimulation induced primary hepatocyte lipid accumulation is obviously reduced, i.e., the PSMB8 gene can promote the development and progression of fatty liver and related diseases; in an HFHC (high fat and high cholesterol) induced WT mouse fatty liver disease model, PR-957 can obviously inhibit HFHC induced weight increase, white grease increase and liver lipidaccumulation; the development and progression of the fatty liver and related diseases are inhibited. Therefore the PSMB8 provides a target for developing medicine for preventing, relieving and / or treating the fatty liver and related diseases.

Description

technical field [0001] The invention belongs to the field of gene function and application, and particularly relates to the application of an immunoproteasome subunit PSMB8 as a drug target in the screening of drugs for the treatment of fatty liver, and the use of PSMB8 inhibitors in the preparation of prevention, alleviation and / or treatment of fatty liver and Drug application in related diseases. Background technique [0002] Fatty liver refers to the lesion of excessive fat accumulation in liver cells caused by various reasons, and is a common clinical phenomenon. Its clinical manifestations are asymptomatic in mild cases, and violent in severe cases. Generally speaking, fatty liver is a reversible disease, early diagnosis and timely treatment can often return to normal. Fatty liver includes alcoholic liver disease and nonalcoholic fatty liver disease, both of which are common chronic liver diseases worldwide. Nonalcoholic fatty liver disease is a metabolic stress dise...

Claims

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Application Information

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IPC IPC(8): C12Q1/6883C12Q1/6886G01N33/574G01N33/573A61K45/00A61P1/16A61P35/00
CPCA61K45/00C12Q1/6883C12Q1/6886C12Q2600/178G01N33/573G01N33/57438
Inventor 李红良
Owner 武汉惠康达科技有限公司
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