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ACSL4 and application thereof in NASH

A technology of drugs and inhibitors, applied in the field of ACSL4 and its application in NASH, can solve the problems that limit the development of chronic liver disease treatment methods and complex effects, and achieve the effect of improving liver lipid accumulation

Pending Publication Date: 2020-07-14
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It is worth noting that TGF-β has a wide range of effects and complex effects, and plays different roles at different stages of disease progression
Simple inhibition of TGF-β can lead to a variety of systemic adverse reactions, limiting the development of TGF-β-targeted treatments for chronic liver diseases

Method used

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  • ACSL4 and application thereof in NASH
  • ACSL4 and application thereof in NASH
  • ACSL4 and application thereof in NASH

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Such as figure 1 Shown is the GEO database (GSE48452, GSE63067, GSE89632) analysis showing that ACSL4 expression was significantly higher in NASH patients than in controls (Panels A-C). For the above database analysis results, a diet-induced NASH mouse model was used for verification. The mice were fed with MCD feed for 8 weeks, and the expression of ACSL4 was detected by Western blot. It was found that the expression of ACSL4 was significantly up-regulated in the diet-induced NASH mouse model compared with the control group, which was consistent with the database analysis results (Figure D).

Embodiment 2

[0035] Such as figure 2 As shown, we constructed ACSL4 liver-specific knockout mice (ACSL4 f / f ; AlbCre + ), fed with MCD feed for 8 weeks, and the histopathological changes and fibrosis of the liver were detected by HE staining and Masson staining. The results showed that compared with the control group, ACSL4 f / f ; AlbCre + Lipid accumulation and liver fibrosis in the mouse liver were significantly improved (Panel A). Then, qPCR method was used to detect the expression of fibrosis and inflammation-related genes, and it was found that ACSL4 f / f ; AlbCre + Genes associated with fibrosis and inflammation were significantly downregulated in mouse livers (Panels B–F).

Embodiment 3

[0037] Such as image 3 As shown, the detection results of serum biochemical indicators showed that in the NASH model induced by MCD feed feeding for 8 weeks, ACSL4 f / f ; AlbCre + Blood triglycerides, low-density lipoprotein, high-density lipoprotein, and AST in mice were significantly improved (Figure A-F), and liver enlargement was reduced (Figure G). Since the MCD diet itself led to a decrease in body weight and blood glucose in mice, no significant changes in body weight and blood glucose-related indicators were detected (Fig. H-I). The above results suggest that liver-specific knockout of ACSL4 can significantly improve the abnormal blood lipids and liver function that usually accompany the progression of NASH.

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Abstract

The invention relates to an application of ACSL4 in selection of NASH drugs, in preparation of NASH drugs and in preparation of NASH diagnostic drugs, and an application of an ACSL4 inhibitor in preparation of drugs for treating or preventing NASH. The ACSL4 inhibitor is a molecule inhibitor for lowering ACSL4 expression level in liver cells, or an enzyme activity inhibitor or a molecule inhibitorfor blocking an ACSL4 acting pathway in the liver cells. According to the application, the clinical significance of ACSL4 in NASH treatment is illustrated, and a wide application prospect for developing ACSL4 as NASH treatment, detection, diagnosis and drug screening target points is provided.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to an ACSL4 and its application in NASH. Background technique [0002] Nonalcoholic fatty liver disease (NAFLD) is a metabolic stress-induced liver injury closely related to insulin resistance and genetic susceptibility. Cirrhosis and hepatocellular carcinoma. At present, NAFLD is a global epidemic trend, and it is one of the causes of increasing liver cirrhosis and liver cancer. It has become the world's first recognized chronic liver disease. It has been reported in the literature that the global prevalence of NAFLD is 25.24%, and the prevalence is increasing year by year. The epidemiological survey results from Shanghai, Beijing and other regions showed that the prevalence of NAFLD diagnosed by B-mode ultrasound in ordinary adults increased from 15% to more than 31% within 10 years. Cardiovascular disease, malignancy, and decompensated liver cirrhosis are common causes o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61P1/16
CPCA61K45/00A61P1/16
Inventor 杨勇孙宏斌段静李娴静王卓
Owner CHINA PHARM UNIV
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