药物性肝损伤与免疫性肝损伤肝组织中lncRNA表达谱的差异分析

Differential expression profile of long non-coding RNA in hepatic tissue between drug-induced liver injury and immune liver injury

目的:研究长链非编码RNA(lncRNA)在药物性肝损伤及免疫性肝损伤中表达谱的变化,并分析二者的差异。方法:利用lncRNA芯片技术分别检测对乙酰氨基酚诱导的小鼠药物性肝损伤及刀豆蛋白A诱导的小鼠免疫性肝损伤肝组织的lncRNA表达谱,通过对原始数据进行预处理达到均一化后,筛选出差异表达lncRNA并进行分析。结果:与正常肝脏组织比较,变化1.5倍以上并且差异有统计学意义(P<0.05)的lncRNA被认为是差异表达的lncRNA;药物性肝损伤肝组织中变化1.5倍以上的共68条,其中升高1.5倍以上的共21条,降低1.5倍以上的共47条;免疫性肝损伤肝组织中变化1.5倍以上的共60条,其中升高1.5倍以上的共17条,降低1.5倍以上的共43条。所有的lncRNA中有8条lncRNA同时在2种肝损伤肝组织中上调,在药物性肝损伤肝组织上调的lncRNA中占38%,在免疫性肝损伤肝组织中占47%;有28条lncRNA同时在2种肝损伤肝组织中下调,在药物性肝损伤肝组织下调的lncRNA中占59%,在免疫性肝损伤肝组织中占65%。结论:与正常肝脏组织比较,药物性肝损伤肝组织和免疫性肝损伤肝组织中lncRNA表达谱均发生明显变化,且2种不同肝损伤肝组织比较,lncRNA表达谱也存在差异,提示2种肝损伤肝组织中这些同时上、下调的lncRNA可能参与了2种肝损伤之间相似或是相同的病理生理过程,而那些表达不同的lncRNA可能参与相对特异的肝损伤机制的发生。

AIM： To analyze the expression profile of long non-coding RNA（ lncRNA） in the liver tissues of drug-induced liver injury（ DILI） and immune liver injury（ ILI）. METHODS： The technique of lncRNA microarray was used to inspect the lncRNA expression profile in the mouse liver tissues that the liver injury was induced by acetaminophen or concanavalin A. The raw data of lncRNA were pretreated for normalization. RESULTS： Compared with normal hepatic tissue,the lncRNA which had more than 1. 5-fold variation and significant difference（ P〈0. 05） by statistical analysis were regarded as lncRNA with differential expression. A total of 68 lncRNA with differential expression were found in the hepatic tissues of DILI,with 21 increased more than 1. 5 folds and 47 reduced more than 1. 5 folds. A total of 60 lncRNA with differential expression in the liver tissues of ILI were observed,with 17 increased more than 1. 5 folds and 43 reduced more than 1. 5 folds. In all lncRNA,8 was simultaneously up-regulated in 2 liver injury models,accounting for 38% and47% respectively,while 28 was simultaneously down-regulated in 2 liver injury models,accounting for 59% and 65% respectively. CONCLUSION： lncRNA expression profiles of DILI and ILI change significantly in comparison with normal hepatic tissue,and there are also differences between 2 hepatic damage models. The simultaneous changes of lncRNA may participate in the same or similar pathophysiological process,while the differences may be involved in relatively particular mechanisms.