A kind of tirna-val antisense chain inhibitor and application thereof

A technology of inhibitor and antisense strand, applied in the field of biomedicine

Active Publication Date: 2021-04-23
THE FIRST AFFILIATED HOSPITAL OF GUANGXI MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the role and molecular mechanism of these tiRNAs in the development of NASH have rarely been reported.

Method used

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  • A kind of tirna-val antisense chain inhibitor and application thereof
  • A kind of tirna-val antisense chain inhibitor and application thereof
  • A kind of tirna-val antisense chain inhibitor and application thereof

Examples

Experimental program
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Embodiment 1

[0019] (1) NASH model construction and related index detection

[0020] According to the method of Tsuchida et al., wild-type mice (C57BL / 6 male mice) were used to construct the NASH model. WD group: Wild-type mice were given Western diet (WD, high-sugar and high-fat diet), fed for 12 weeks, and injected intraperitoneally once a week with carbon tetrachloride (CCl 4 ) induces hepatitis and fibrosis. ND group: wild-type mice were fed with control diet (control group) for 12 weeks, and corn oil was injected intraperitoneally once a week. 6 in each group.

[0021]Collect serum, detect liver function indicators (AST and ALT), inflammatory factors (IL-6, TNF-α, TGF-, etc.), triglycerides, complements (C3a, C5a), etc.; take liver tissue to prepare wax blocks, and use H&E , Sirius red staining, etc. to detect liver tissue morphology; fresh liver tissue was frozen and stained with Oil Red O to detect fatty degeneration, etc.; liver tissue was taken from mice to detect liver tissue ...

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Abstract

The invention discloses a tiRNA-Val antisense chain inhibitor and application thereof. The present invention utilizes a mouse model of non-alcoholic steatohepatitis, performs tRFs sequencing on liver tissue, and analyzes and screens to obtain tiRNA-Val whose expression level is significantly up-regulated compared with that of the control group. By synthesizing a chemically modified tiRNA-Val antisense chain inhibitor, the in vivo experiment of non-alcoholic steatohepatitis mice was carried out. The results showed that after inhibiting tiRNA-Val in mice, the liver function indicators ALT and AST decreased; the pathological results showed that the liver The oil droplets in the liver became significantly smaller, and the number also decreased significantly; the triglycerides in the liver tissue decreased significantly, and the serum TNF-α level decreased. It shows that selective and effective intervention targeting tiRNA-Val, such as the use of tiRNA-Val antisense chain inhibitors, can improve lipid metabolism, reduce inflammatory responses, and prevent or slow down the occurrence and development of NASH.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to a tiRNA-Val antisense chain inhibitor and application thereof. Background technique [0002] Nonalcoholic fatty liver disease (NAFLD) is a liver disease that develops from simple steatosis (nonalcoholic fatty liver, NAFL) to steatohepatitis (nonalcoholic steatohepatitis, NASH), fat Liver fibrosis, cirrhosis, and even clinical syndromes of hepatocellular carcinoma. It is predicted that the adult prevalence rate of NAFLD is about 25% in the world, and 20%-40% in developed countries in Europe and America. NAFLD manifests as fatty liver in the early stage, and about 25% of the patients can further develop into NASH. In addition to the morbidity and mortality associated with the liver, NAFLD is also closely related to several other extrahepatic diseases such as type 2 diabetes and hyperlipidemia, which are very harmful. Notably, NAFL and NASH are not only present in ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/06A61K31/7088A61P3/06A61P1/16C12N15/113
CPCA61K31/7088A61K45/06A61P1/16A61P3/06C12N15/113
Inventor 钟伏弟江克清何松青金虎丁瑾王思凡
Owner THE FIRST AFFILIATED HOSPITAL OF GUANGXI MEDICAL UNIV
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