Inhibition of Endoplasmic Reticulum Stress Attenuated Ethanol-Induced Exosomal miR-122 and Acute Liver Injury in Mice.
Alcohol Alcohol
; 54(5): 465-471, 2019 Jan 09.
Article
em En
| MEDLINE
| ID: mdl-31361816
ABSTRACT
AIMS:
In acute alcoholic liver injury, alcohol can directly or indirectly induce endoplasmic reticulum stress (ERS) to participate in liver injury, and it is found that the expression of serum exosomal miR-122 is significantly affected. Therefore, the present study investigated the effects of endoplasmic reticulum stress inhibition on the expression of serum exosomal miR-122 and acute liver injury.METHODS:
The acute alcoholic liver injury models were established by the intragastric administration of ethanol (5 g/kg) in ICR mice. Intervention group received 4-phenylbutyric acid (PBA, endoplasmic reticulum stress inhibitor; 75 mg/kg and 150 mg/kg, intraperitoneal) 12 and 24 hours before intragastric administration. Mice treated with saline were used as controls.RESULTS:
The ethanol treated mice exhibited significantly elevated hepatosomatic index (liver weight/body weight) and alanine aminotransferase (ALT), compared with those in the control group (P < 0.05). The ERS inhibitor 4-phenylbutyric acid protected against ethanol induced acute liver injury and hepatocyte necrosis, and PBA 150 mg/kg significantly attenuated ethanol induced hepatic ER stress-related proteins (GRP78, pIRE1α and pIF2α) (P < 0.05). Moreover, PBA 150 mg/kg markedly alleviated ethanol induced elevation of hepatic and serum exosomal miR-122 and pri-miR-122 (P < 0.05).CONCLUSIONS:
These findings suggest that ER stress inhibitor PBA attenuated ethanol induced acute liver injury and serum exosomal miR-122, and provides a potential therapy strategy for acute alcoholic liver injury.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Fenilbutiratos
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MicroRNAs
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Etanol
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Exossomos
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Doença Hepática Induzida por Substâncias e Drogas
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Estresse do Retículo Endoplasmático
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article