氟西汀在慢性丙型肝炎抗病毒治疗中的作用

秦源; 张颖; 赵洁茹; 郭永红; 贾战生

doi:10.3969/j.issn.1001-5256.2016.09.036

氟西汀在慢性丙型肝炎抗病毒治疗中的作用

DOI: 10.3969/j.issn.1001-5256.2016.09.036

1. 第四军医大学唐都医院全军感染病诊疗中心
2. 西安交通大学医学院第二附属医院感染科

基金项目:

国家自然科学基金(81273218)；

详细信息

中图分类号: R512.63
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出版历程
- 出版日期: 2016-09-20

The role of fluoxetine in antiviral therapy for chronic hepatitis C

Center of Diagnosis and Treatment for Infectious Diseases of PLA, Tangdu Hospital, Fourth Military Medical University

Research funding:

摘要

摘要:
超过20%的慢性丙型肝炎(CHC)患者接受IFNα抗病毒治疗后出现抑郁症,氟西汀常用于缓解此症状。氟西汀具有抗炎特性,可改变肝脏脂质合成,但其对CHC抗病毒治疗的影响及机制仍未阐明。近期研究表明氟西汀可抑制HCV感染Huh7.5细胞,且缓解了胞内活性氧生成和脂质蓄积,并通过激活STAT1和JNK通路促进IFNα介导的抗病毒作用,降低患者HCV载量及ALT水平。此外,氟西汀增强了CHC患者过氧化物酶体增殖物激活受体(PPAR)反应元件活性,其对HCV感染和脂质蓄积的抑制效应可被PPARβ/γ等拮抗物一定程度逆转,表明氟西汀可能通过调节PPARβ/γ和JNK/STAT通路抑制HCV感染、活性氧生成及脂质蓄积。
- 肝炎,丙型,慢性 /
- 氟西汀 /
- 药理作用分子作用机制 /
- 综述
Abstract:
More than 20% of chronic hepatitis C( CHC) patients receiving the antiviral therapy with interferonα( IFNα) experience depression,and fluoxetine is often used to alleviate this symptom. Fluoxetine has anti- inflammatory properties and can change the synthesis of liver lipids,but its influence on antiviral therapy for CHC and related mechanism remain unknown. Recent studies show that fluoxetine can inhibit hepatitis C virus( HCV) infection and reduce the production of reactive oxygen species( ROS) and lipid accumulation in Huh7. 5cells; in addition,it can promote the antiviral effect mediated by IFNα through activating STAT1 and JNK signaling pathways and thus reduce HCV viral load and the level of alanine aminotransferase in CHC patients. Fluoxetine elevates PPAR response element activity in CHC patients,and its inhibitory effect on HCV infection and lipid accumulation were partly reversed by antagonists including PPARβ/γ,suggesting that fluoxetine inhibits HCV infection,ROS production,and lipid accumulation through regulating PPARβ/γ and JNK/STAT pathways.
- hepatitis C,chronic /
- fluoxetine /
- molecular mechanisms of pharmacological action /
- review

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参考文献(35)

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