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细胞色素 P450 衍生的类二十烷酸和肝脏疾病中的炎症。

Cytochrome P450-derived eicosanoids and inflammation in liver diseases.

机构信息

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.

出版信息

Prostaglandins Other Lipid Mediat. 2020 Apr;147:106400. doi: 10.1016/j.prostaglandins.2019.106400. Epub 2019 Nov 14.

Abstract

Hepatic inflammation is a key pathologic mediator in a wide array of acute and chronic liver diseases. Hepatitis is a crucial driver of liver tissue damage provoking the progression to severe fibrosis, cirrhosis and hepatocellular carcinoma, irrespective of the etiologic cause. Inflammatory liver diseases are collectively considered one of the most critical public health risks. Cytochrome P450 (CYP) enzymes are superfamily of monooxygenases which possess the greater diversity of substrate structures amidst all other enzyme families. Members of omega-3 as well as omega-6 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid and arachidonic acid, respectively, can be metabolized by CYP isoforms leading to the production of biologically active lipid mediators called eicosanoids. CYP-derived eicosanoids have been shown to play significant roles in the pathophysiology and protection of multiple inflammatory liver diseases. In this review, we elucidate the intricate role of CYP-derived eicosanoids in inflammation in liver diseases paving the way for better therapeutic approaches.

摘要

肝炎症是广泛的急性和慢性肝病的关键病理介质。肝炎是肝脏组织损伤的关键驱动因素,促使其进展为严重纤维化、肝硬化和肝细胞癌,无论病因如何。炎症性肝病被普遍认为是最严重的公共健康风险之一。细胞色素 P450(CYP)酶是单加氧酶超家族,在所有其他酶家族中具有最多样化的底物结构。ω-3 和 ω-6 多不饱和脂肪酸(PUFA)的成员,如二十碳五烯酸和花生四烯酸,分别可以被 CYP 同工酶代谢,产生称为类二十烷酸的生物活性脂质介质。CYP 衍生的类二十烷酸已被证明在多种炎症性肝病的病理生理学和保护中发挥重要作用。在这篇综述中,我们阐明了 CYP 衍生的类二十烷酸在肝脏疾病炎症中的复杂作用,为更好的治疗方法铺平了道路。

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