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Application of FXR agonist in treatment of hepatic encephalopathy

A technology of hepatic encephalopathy and agonists, applied in the field of biomedicine, can solve the problems that the application of OCA has not been reported yet

Active Publication Date: 2020-09-22
HENAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] OCA was successfully developed by Intercept Pharmaceutical Company of the United States. It is the first drug developed for the treatment of cholestatic liver disease in the past two decades. As a bile acid mimic, it can activate FXR. However, there is no information about the application of OCA in hepatic encephalopathy. see the report

Method used

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  • Application of FXR agonist in treatment of hepatic encephalopathy
  • Application of FXR agonist in treatment of hepatic encephalopathy
  • Application of FXR agonist in treatment of hepatic encephalopathy

Examples

Experimental program
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Embodiment 1

[0021] The materials and reagents used in the following examples can be obtained from commercial sources unless otherwise specified.

[0022] 12-week-old wild-type C57BL / 6N male mice: purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd., C57BL / 6N FXR-deficient mice: purchased from the City of Hope Medical Center Laboratory in the United States; obeticholic acid ( OCA): purchased from Taosu, catalog number 459789-99-2; methylcellulose: purchased from Taosu, catalog number 9004-67-5; thioacetamide (TAA): purchased from Taosu , catalog number 62-55-5; NH 3 , ALB, ALT, AST, TBA, ALP, BUN and other detection kits: purchased from Fuji, Japan; GFPA antibody: purchased from abcam, catalog number is ab183735; immunohistochemical secondary antibody kit: purchased from Zhongshan Jinqiao, PV -9001.

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Abstract

The invention belongs to the technical field of biological medicine, and particularly relates to application of an FXR agonist in treatment of hepatic encephalopathy, particularly to application of obeticholic acid in treatment of hepatic encephalopathy. The invention also provides the application of the nuclear receptor FXR in treatment of hepatic encephalopathy, and particularly, a drug for treating hepatic encephalopathy or protecting the liver is obtained through adoption of the nuclear receptor FXR as a target spot. The FXR is activated by an FXR agonist obeticholic acid (OCA), and in a liver injury model, expression of NAGS, SLC1A4, AL and other key enzymes of ammonia metabolic pathways is induced through activation of the FXR, the content of blood ammonia in blood can be reduced, and injuries to brain astrocyte are reduced; and moreover, through the liver can be protected significantly through activation of the FXR.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of FXR agonists in the treatment of hepatic encephalopathy. Background technique [0002] Hepatic encephalopathy (hepatic encephalopathy, HE) is a reversible metabolic disease caused by central nervous system dysfunction in patients with acute or chronic liver disease. The pathogenesis of hepatic encephalopathy is relatively complicated, and the theory of ammonia poisoning has been dominant in its pathogenesis hypothesis for a long time. Intestinal-derived toxins such as blood ammonia are metabolized and eliminated by the liver under normal circumstances, but in the case of liver failure and abnormal portosystemic shunt, ammonia and other toxins cannot be eliminated by liver metabolism and directly enter the systemic circulation, and then penetrate the blood -The brain barrier enters the brain, leading to the occurrence of neuropsychiatric symptom...

Claims

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Application Information

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IPC IPC(8): C12Q1/6883G01N33/68A61K31/575A61K45/06A61K48/00A61P1/16A61P25/00
CPCA61K31/575A61K45/06A61K48/0025A61P1/16A61P25/00C12Q1/6883C12Q2600/158G01N33/6893G01N2800/085
Inventor 陈卫东叶文凌王艳东周云赵世振白校杰赵阳
Owner HENAN UNIVERSITY
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