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Macrophage-targeted mTORC1 activator for controlling NASH progression

A macrophage, active technology, applied in the field of biomedicine, can solve the problem of unknown role of mTORC1

Inactive Publication Date: 2018-02-16
TIANJIN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Currently, the role of mTORC1 in macrophages in NASH is unknown

Method used

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  • Macrophage-targeted mTORC1 activator for controlling NASH progression
  • Macrophage-targeted mTORC1 activator for controlling NASH progression
  • Macrophage-targeted mTORC1 activator for controlling NASH progression

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Example 1. Research on the role of mTORC1 in macrophages in nonalcoholic steatohepatitis

[0054] 1. Increased activity of mTORC1 in liver macrophages of NASH patients

[0055]The liver samples of 5 mild NASH patients and 5 severe NASH patients were obtained from their liver biopsy samples, and the liver biopsy samples of 6 normal individuals were obtained from the evaluation of their suitability as liver donors. The degree of NASH was judged by pathologists based on H&E staining. S6 is the canonical downstream of mTORC1, and its increased phosphorylation reflects the increased activity of mTORC1. We used immunofluorescence to mark macrophages with CD68 in human liver slices, and simultaneously detected the pS6 content in macrophages in the livers of normal people and NASH patients. We found that the content of pS6 in macrophages in liver slices of mild NASH patients was significantly higher than that of normal people, and the content of pS6 in liver macrophages of pa...

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PUM

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Abstract

The invention discloses a macrophage-targeted mTORC1 activator for controlling NASH progression. The invention provides the application of a substance capable of reducing the activity of mTORC1 in macrophages in the preparation of a product capable of promoting progression of non-alcoholic steatohepatitis to hepatic fibrosis. By studying the effect of mTORC1 in macrophages on the non-alcoholic steatohepatitis, it is found that the progression of non-alcoholic steatohepatitis can be accelerated by inhibiting the activity of mTORC1 in macrophages. The invention is of great reference significancefor the research on the pathogenesis of non-alcoholic steatohepatitis and for the selection of future treatment strategies.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to an mTORC1 activator targeting macrophages for controlling the progress of NASH. Background technique [0002] Non-alcoholic fatty liver disease (NAFLD) is a disease characterized by fat accumulation in the liver and includes a series of histological changes, mainly including simple hepatic steatosis, nonalcoholic steatohepatitis (nonalcoholic steatohepatitis) steatohepatitis, NASH), liver fibrosis, cirrhosis and liver cancer. Its incidence is 30% in developed countries, nearly 10% in developing countries, 20-30% in the general population, and 75-100% in obese people. It is currently considered the most common liver disease and can develop into end-stage Liver Disease. Obesity, hypertension, dyslipidemia and insulin resistance are closely related to NAFLD. Simple hepatic steatosis can be reversed to a normal liver, but after progressing to NASH, steatosis will be accompanied by inflamm...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K49/00A61P1/16
CPCA61K45/00A61K49/0008
Inventor 朱毅艾玎王春炅刘雯丽叶晨吉
Owner TIANJIN MEDICAL UNIV
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