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Application of O-GlcNAc glycosylation modification in preventing and treating hepatic fibrosis

A technology of liver fibrosis and glycosylation, applied in the fields of biotechnology and medicine

Active Publication Date: 2016-03-30
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] However, the changes of O-GlcNAc glycosylation in liver fibrosis, the effect of O-GlcNAc glycosylation on the process of liver fibrosis, and the strategies for treating and / or preventing liver fibrosis based on O-GlcNAc glycosylation and no relevant reports

Method used

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  • Application of O-GlcNAc glycosylation modification in preventing and treating hepatic fibrosis
  • Application of O-GlcNAc glycosylation modification in preventing and treating hepatic fibrosis
  • Application of O-GlcNAc glycosylation modification in preventing and treating hepatic fibrosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0149] Example 1. N-acetylglucosamine pretreatment inhibits TAA-induced liver fibrosis in mice

[0150] In order to detect whether N-acetylglucosamine has a protective effect on liver fibrosis caused by thioacetamide (TAA), the inventor constructed a TAA mouse model of liver fibrosis, and used different doses of N-acetyl Glucosamine was injected intraperitoneally, and the protective effect of N-acetylglucosamine on the pathomorphology and liver function of liver fibrosis caused by TAA was observed.

[0151] Modeling and dosage:

[0152] group

drug

Dosage

Dosing frequency

T

TAA

200mg / kg / time

3 times a week

L

N-Acetyl Glucosamine Low Dose

50mg / kg / day

1 dose per day

H

N-acetylglucosamine high dose

200mg / kg / d

1 dose per day

S

Silymarin

25mg / kg / day

1 dose per day

[0153] Among them, the TAA, N-acetylglucosamine and silymarin used were all purchased from Sigma Company, and the...

Embodiment 2

[0196] Example 2. Glucosamine pretreatment inhibits TAA-induced liver fibrosis in mice

[0197] In order to detect whether glucosamine has a protective effect on liver fibrosis caused by thioacetamide (TAA), the inventors constructed a TAA mouse model of liver fibrosis. To observe the protective effect of glucosamine on the pathological morphology and liver function of liver fibrosis caused by TAA.

[0198] Modeling and dosage:

[0199] group

drug

Dosage

Dosing frequency

T

TAA

200mg / kg / time

3 times a week

L

low dose glucosamine

60mg / kg / day

1 dose per day

H

Glucosamine High Dose

300mg / kg / day

1 dose per day

S

Silymarin

25mg / kg / day

1 dose per day

[0200] Among them, the TAA, glucosamine and silymarin used were all purchased from Sigma Company, the batch numbers were: 163678-25G; G4875-25G; S0292.

[0201] Animal grouping and dosing:

[0202] Healthy Balb / C mice, male, 4...

Embodiment 3

[0243] Example 3.O-linked N-acetylglucosaminidase (OGA) inhibitor PugNAc pretreatment inhibits TAA induction liver fibrosis in mice

[0244] In order to detect whether the OGA inhibitor PugNAc has a protective effect on liver fibrosis caused by thioacetamide (TAA), the inventors first constructed a TAA mouse liver fibrosis model, and injected different doses of PugNAc intraperitoneally while performing TAA modeling , and observe the protective effect of PugNAc on the pathological morphology of liver fibrosis caused by TAA and the expression and distribution of α-smooth muscle actin (α-SMA).

[0245] Modeling and dosage:

[0246] group

drug

Dosage

Dosing frequency

T

TAA

200mg / kg / time

3 times a week

L

PugNAc Low Dose

50mg / kg / day

1 dose per day

H

PugNAc High Dose

100mg / kg / day

1 dose per day

S

Silymarin

25mg / kg / day

1 dose per day

[0247] Among them, the TAA, PugNAc and sil...

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PUM

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Abstract

The invention provides an application of O-GlcNAc glycosylation modification in preventing and treating hepatic fibrosis. In the invention, excessive activation and proliferation of hepatic stellate cells as well as the expression of alpha-smooth muscle actin and I-type collagen and the formation of fibrous septum can be inhibited by enhancing O-GlcNAc glycosylation modification, and the O-GlcNAc glycosylation modification has a good application prospect in preventing and / or treating hepatic fibrosis.

Description

technical field [0001] The invention belongs to the fields of biotechnology and medicine. Specifically, the present invention relates to the application of O-GlcNAc glycosylation modification in the treatment and / or prevention of liver fibrosis. Background technique [0002] Liver fibrosis is a histological change in the late stage of chronic liver disease and a progressive pathological process under the continuous action of inflammatory factors. Due to the abnormal excessive deposition of extracellular matrix in the liver, fibrous septa are formed, the original structure of the liver is destroyed, and liver fibrosis is caused. Liver fibrosis is also a dynamic process involving a variety of cells and cytokines. Cytokines form a huge network system with intrahepatic cells and extracellular matrix, and regulate the occurrence and development of liver fibrosis. [0003] Hepatic stellate cells (HSCs) play a decisive role in liver fibrosis. The activation of hepatic stellate c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K45/06A61K31/7008A61P1/16
CPCA61K31/7008A61K45/00A61K45/06
Inventor 顾建新阮元元贾冬威宋淑淑邵苗苗李莉莉
Owner FUDAN UNIV
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