Application of SAA inhibitor in preparation of medicine for treating acute liver injury, acute liver failure or acute-on-chronic liver failure

A technology for acute liver failure and acute liver injury, which is applied in the field of biomedicine to achieve the effects of enhancing damage, promoting adhesion, and promoting liver damage

Pending Publication Date: 2020-11-13
GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is no report on the role and molecular mechanism of SAA1/2 in the process of APAP-induced liver injury
[0004] In view of the general lack of effective drugs for the tre

Method used

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  • Application of SAA inhibitor in preparation of medicine for treating acute liver injury, acute liver failure or acute-on-chronic liver failure
  • Application of SAA inhibitor in preparation of medicine for treating acute liver injury, acute liver failure or acute-on-chronic liver failure
  • Application of SAA inhibitor in preparation of medicine for treating acute liver injury, acute liver failure or acute-on-chronic liver failure

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] This example explores the expression behavior of serum amyloid A (SAA1 / 2) in the process of acute liver injury in mice, the operation is as follows:

[0066] (1) To construct an APAP-induced acute liver injury model in mice, the specific method is: use 8-week-old BALB / c strain mice, fast for 6 hours before injecting APAP drugs, and then inject APAP intraperitoneally at a dose of 400 mg / kg , the APAP-induced acute liver injury model can be established. Subsequently, samples were collected at 6 hours, day 1, day 3, and day 7 after injury, including heart blood collection, and paraffin-embedded and frozen liver tissues were collected for subsequent experiments.

[0067] (2) Liver tissue immunohistochemical staining method to detect the expression level of SAA1 / 2, the specific method is:

[0068] Liver tissues were collected at different time points after APAP-induced liver injury in mice, fixed in paraformaldehyde solution for 24 hours, and then dehydrated, embedded and s...

Embodiment 2

[0079] This example explores that serum amyloid A (SAA1 / 2) can enhance the damage effect of APAP on hepatic sinusoidal endothelial cells, and the operation is as follows:

[0080] (1) The death of primary hepatic sinusoidal endothelial cells induced by APAP at a concentration of 10, 20 and 30 mM was detected by flow cytometry, and the method was carried out according to the instruction manual of FITC Annexin V Apoptosis Detection Kit I (Cat.556547) of BD Company , the result is as Figure 8 shown by Figure 8 It can be seen that different concentrations of APAP can significantly induce the death of hepatic sinusoidal endothelial cells after stimulating hepatic sinusoidal endothelial cells for 6 hours, and it is concentration-dependent. DMSO was used as the control.

[0081] (2) The death of primary hepatic sinusoidal endothelial cells induced by APAP combined with SAA1 / 2 (3 μg / mL) at a concentration of 10 mM was detected by flow cytometry, and the method was referred to the F...

Embodiment 3

[0083] This example explores the ability of serum amyloid A (SAA1 / 2) to promote the adhesion of platelets on sinusoidal endothelial cells, the operation is as follows:

[0084] The isolated primary sinusoidal endothelial cells were cultured in vitro for 48 to 72 hours until the cell confluency reached 100%, then the sinusoidal endothelial cells were stimulated with DMSO, APAP, SAA1 / 2 and APAP+SAA1 / 2 for 2 hours, and then the freshly isolated Platelets (labeled with Di1 red dye) were co-cultured with sinusoidal endothelial cells for 2 hours, and then washed with PBS to remove unadhered platelets and then photographed, as shown in Figure 11 (the scale bar in the figure is 50 μm); the fluorescence intensity statistics of the adhered platelets, as shown in Figure 12 shown by Figure 12 It can be seen that SAA1 / 2 stimulation alone can promote the adhesion ability of platelets on sinusoidal endothelial cells.

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Abstract

The invention relates to application of a serum amyloid protein A inhibitor in preparing a medicine for treating acute liver injury, acute liver failure or acute-on-chronic liver failure. The serum amyloid protein A inhibitor is used for blocking SAA1/2, so that the APAP-induced liver injury degree can be remarkably reduced, the repair process after injury can be enhanced, and the level of glutamic-pyruvic transaminase (ALT) and/or glutamic oxalacetic transaminase (AST) in blood can be reduced; the effect of inhibiting SAA1/2 can reduce intrahepatic hemorrhage induced by APAP and aggregation of platelets in the liver. Therefore, the serum amyloid protein A inhibitor can be applied to preparation of medicines for treating acute liver injury, acute liver failure or acute-on-chronic liver failure; a new strategy is provided for treatment of acute liver injury, acute liver failure or acute-on-chronic liver failure, the strategy can make up for the defects that in the prior art, an NAC treatment method is short in window period and large in side effect, and a liver transplantation method is short in donor, immunological rejection and the like to a certain extent, and the method has thecharacteristics of low immunogenicity, low cost and the like.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, relates to a new strategy for treating acute liver injury, acute liver failure or acute-on-chronic liver failure, and particularly relates to the preparation of serum amyloid A inhibitors for the treatment of acute liver injury, acute liver failure or chronic liver failure. Application of drugs in exacerbation of acute liver failure. Background technique [0002] Acute liver failure is the end stage of severe liver damage caused by a variety of factors. Liver cell death leads to dysfunctions such as synthesis, detoxification, excretion and biotransformation of the liver that cannot be compensated, and coagulation dysfunction, jaundice, hepatic encephalopathy, ascites, etc. Severe hepatic syndrome. Acute liver failure is mainly caused by factors such as hepatitis virus (mainly hepatitis B virus HBV), drugs (mainly acetaminophen) and hepatotoxic substances (such as alcohol, chemical agents and...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K39/395A61K38/10A61K45/06A61P1/16
CPCA61K45/00A61K39/3955A61K38/10A61K45/06A61P1/16A61K2300/00
Inventor 李尹雄游凯
Owner GUANGZHOU INST OF BIOMEDICINE & HEALTH CHINESE ACAD OF SCI
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