Qu Dong, Zhang Kaikai, Chen Lijian, Wang Qi, Wang Huijun
Department of Forensic Pathology, School of Forensic Medicine, Southern Medical University, Guangzhou, China.
PeerJ. 2020 Feb 6;8:e8529. doi: 10.7717/peerj.8529. eCollection 2020.
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.
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。