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木犀草素对大鼠甲基苯丙胺诱导的肝毒性影响的RNA测序分析:一项初步研究。

RNA-sequencing analysis of the effect of luteolin on methamphetamine-induced hepatotoxicity in rats: a preliminary study.

作者信息

Qu Dong, Zhang Kaikai, Chen Lijian, Wang Qi, Wang Huijun

机构信息

Department of Forensic Pathology, School of Forensic Medicine, Southern Medical University, Guangzhou, China.

出版信息

PeerJ. 2020 Feb 6;8:e8529. doi: 10.7717/peerj.8529. eCollection 2020.

Abstract

In this study, RNA-sequencing (RNA-seq) was utilized to investigate the effects of luteolin on hepatotoxicity caused by methamphetamine (METH). The rats in METH group were administrated with METH (15 mg/kg, two times per day) via intraperitoneal (i.p.) injections for four consecutive days. The rats in luteolin + METH group were firstly administrated with luteolin (100 mg/kg, once a day) by oral gavage for 3 days before METH treatment. Lueolin attenuated the hepatotoxicity induced by METH via histopathological and biochemical analysis. The results of RNA-seq showed that luteolin could regulate 497 differentially expressed genes (DEGs), and the selected DEGs were mainly enriched in eight pathways, according to KEGG analysis. Furthermore, qRT-PCR was utilized to verify the results of RNA-seq. Six genes were selected as follows: liver enriched antimicrobial peptide 2 (Leap2), fatty acid synthase (Fasn), fatty acid binding protein 5 (Fabp5), patatin like phospholipase domain containing 3 (Pnpla3), myelin basic protein (Mbp) and calmodulin 3 (Calm3). Though because of the design flaws, the luteolin group has not been included, this study demonstrated that luteolin might exert hepato-protective effects from METH via modulation of oxidative phosphorylation, cytochrome P450 and certain signaling pathways.

摘要

在本研究中,利用RNA测序(RNA-seq)来研究木犀草素对甲基苯丙胺(METH)所致肝毒性的影响。METH组大鼠通过腹腔注射给予METH(15mg/kg,每天两次),连续四天。木犀草素+METH组大鼠在METH处理前,先通过灌胃给予木犀草素(100mg/kg,每天一次),持续3天。通过组织病理学和生化分析,木犀草素减轻了METH诱导的肝毒性。RNA-seq结果显示,根据KEGG分析,木犀草素可调节497个差异表达基因(DEG),所选的DEG主要富集于8条通路。此外,利用qRT-PCR验证RNA-seq结果。选择了6个基因,分别为:肝脏富集抗菌肽2(Leap2)、脂肪酸合酶(Fasn)、脂肪酸结合蛋白5(Fabp5)、含patatin样磷脂酶结构域3(Pnpla3)、髓鞘碱性蛋白(Mbp)和钙调蛋白3(Calm3)。尽管由于设计缺陷未纳入木犀草素组,但本研究表明木犀草素可能通过调节氧化磷酸化、细胞色素P450和某些信号通路对METH发挥肝脏保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d1a/7007981/ba10edf9a582/peerj-08-8529-g001.jpg

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