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tiRNA-Val antisense strand inhibitor and application thereof

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

Active Publication Date: 2020-09-18
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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  • tiRNA-Val antisense strand inhibitor and application thereof
  • tiRNA-Val antisense strand inhibitor and application thereof
  • tiRNA-Val antisense strand inhibitor and application thereof

Examples

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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 strand inhibitor and an application thereof. According to the present invention, a mice non-alcoholic steatohepatitis model is used to conduct tRFs sequencing on liver tissues, and then tiRNA-Val with significantly up-regulated expression level compared to a control group is obtained by analysis and screening. By synthesizing the chemically modified tiRNA-Val antisense strand inhibitor, a non-alcoholic steatohepatitis mice test is conducted in vivo. The results of the test show that liver function indexes ALT and AST decrease after inhibiting the tiRNA-Val in mice. The pathological results show that oil droplets in the liver are obviously smaller, and the number of the oil droplets is also significantly reduced. The triglyceride in the liver tissues is significantly reduced, and level of serum TNF-alpha is reduced. These results indicate that effective intervention is selectively conducted for the tiRNA-Val, for example, the tiRNA-Val antisense strand inhibitor can be used to improve lipid metabolism, reduce inflammation response, and prevent or retard 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 Applications(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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