基于lncRNA表达谱变化探讨Scoparone对肝损伤的干预效应  

To investigate the intervention effect of Scoparone on liver injury based on the changes of lncRNA expression profile

作　　者：吕建林 潘尚领[1] LYU Jian-lin;PAN Shang-ling(School of Basic Medical Sciences,Guangxi Medical University,Nanning 530021,China;The First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,China)

机构地区：[1]广西医科大学基础医学院,广西南宁530021 [2]广西中医药大学第一附属医院,广西南宁530023

出　　处：《广西大学学报（自然科学版）》2021年第3期778-784,共7页Journal of Guangxi University（Natural Science Edition）

基　　金：国家自然科学基金资助项目(81860839);广西自然科学基金资助项目(2020GXNSFAA238020,2019JJA140342);广西中医基础研究重点实验室开放课题项目(K201137910);广西研究生教育创新计划项目(YCBZ2019035)。

摘　　要：对乙酰氨基酚(APAP)诱导大鼠急性药物性肝损伤,基于大鼠肝脏长链非编码RNA(lncRNA)表达谱的检测,探讨中药茵陈蒿(Artemisia capillaris Thunb)活性成分6,7-二甲氧基香豆素(Scoparone,简称Sco)保护肝损伤的分子机制。将30只大鼠随机分为对照组、模型组和Sco干预组。采用腹腔注射APAP(800 mg/kg)建立急性药物性肝损伤模型;Sco干预组给予Sco(500μmol)灌胃,连续干预5 d后取材;对照组和模型组给予等量橄榄油。给药结束后,收集血清测定生化指标;采用lncRNA基因芯片技术筛选组间肝组织差异表达lncRNAs,并采用实时荧光定量PCR法对lncRNA靶基因表达进行验证。结果表明:大鼠血清ALT、AST和T-BIL含量相对于对照组,模型组显著升高(均P<0.0001)。但Sco干预后,含量均显著下降(均P<0.0001)。筛选组间表达差异倍数大于2且显著的lncRNA,9个lncRNA在模型组显著上调,但Sco干预后显著下调;6个lncRNA在模型组显著下调,但Sco干预后显著上调。相对于对照组,差异表达lncRNA NONRATG 022224.2的靶基因Vdr表达水平显著下降(P<0.001),但Sco干预后,Vdr表达水平显著提高(P<0.01)。Sco对大鼠急性药物性肝损伤具有一定的保护作用,lncRNA NONRATG 022224.2靶向调控Vdr基因可能在Sco保护大鼠急性药物性肝损伤中发挥重要作用。To investigate the molecular mechanism of hepatic injury treatmentby Scoparone(6,7-dimethoxycoumarin,Sco),the active ingredient of Artemisia capillaris Thunb,we explored long non-coding RNA(lncRNA)expression profiles in the liver of rats with APAP(acetaminophen)-induced acute liver injury.Thirty rats were randomly divided into control group,model group and Sco intervention group.The acute drug-induced liver injury model was established by intraperitoneal injection of APAP(800 mg/kg);Sco intervention group was given Sco(500μmol)by gavage and taken after 5 consecutive days of intervention;control and model groups were given equal amounts of olive oil.Serum was collected to determine biochemical indexes;lncRNA gene microarray technology was used to screen differentially expressed lncRNAs in liver tissues between groups;real-time fluorescence quantitative PCR was used to verify the expression of lncRNA target genes.Serum ALT,AST and T-BIL levels of rats were significantly increased in the model group(all P<0.0001)relative to the control group.However,the levels were all significantly decreased after Sco intervention(all P<0.0001).Screening for lncRNAs with expression foldchange between groups greater than 2 and significant expression differences between groups,9 lncRNAs were significantly upregulated in the model group but significantly downregulated after Sco intervention;6 lncRNAs were significantly downregulated in the model group but significantly upregulated after Sco intervention.Relative to the control group,Vdr,target gene of the differentially expressed lncRNA NONRATG022224.2,was significantly decreased(P<0.001),but Vdr expression level was significantly increased after Sco intervention(P<0.01).Sco has a protective effect on acute drug-induced liver injury in rats,and target regulation of Vdr by lncRNA NONRATG022224.2 may play an important role in Sco protection against acute drug-induced liver injury in rats.

关 键 词：急性药物性肝损伤 长链非编码RNA 6 7-二甲氧基香豆素 

分 类 号：R575.5[医药卫生—消化系统]