大鼠酒精性肝损伤模型RNA可变剪切变化分析

Analysis of the variable of alternative splicing in alcoholic liver injury rats

目的了解大鼠酒精性肝损伤模型中RNA的可变剪切变化情况。方法模型组大鼠连续灌服56°白酒8周,对照组给予同等剂量的蒸馏水,采集血液,测定血清丙氨酸氨基转移酶(ALT)及天门冬氨酸氨基转移酶(AST)水平,剖取大鼠肝组织,提取RNA,运用全基因组表达谱芯片检测分析可变剪切变化,采用Gene Ontology(GO)和Pathway富集分析了解差异可变剪切的编码RNA的功能。结果共筛选到4 662个差异可变剪切的RNA(Splicing Index<-3或>3,P<0.05),其中差异可变剪切的编码RNA有3 989个,差异可变剪切的非编码RNA有673个,对差异可变剪切的编码RNA进行GO和Pathway富集分析,结果显示,主要与氧化还原酶活性、氧代谢、外源性转运蛋白活性、脂肪酸的生物合成、脂肪酸的降解、过氧化物酶体、谷胱甘肽代谢等功能或通路有关。结论酒精性肝损伤大鼠模型肝脏组织中存在着大量差异可变剪切的RNA,提示这些RNA的可变剪切可能在肝脏酒精性病变的发生发展中起着重要的作用。

Objective To investigate and understand the variable of alternative splicing in alcoholic liver injury rats.Methods The model group rats were continuous administration of 56 degree white wine for 8 weeks,control group were given the same dose of distilled water,blood were collected for the determination the levels of serum alanine aminotransferase（ALT） and aspartate transaminase（AST）. The hepatic tissue was dissected and RNA was extracted. The alternative splicing variables were detected and analyzed with the whole genome expression chip. The function of differentially alternative splicing coding RNA was analyzed by Gene Ontology（GO） and Pathway enrichment analysis programs. Results A total of 4 662 RNA were screened（Splicing Index〈-3 or 〉3, P〈0.05）; there were 3 989 coded RNA and 673 non-coding RNA had alternative splicing. The GO and Pathway enrichment analysis results indicated that the coded RNAs mainly related to oxidoreductase activity, oxygen metabolism, exogenous transport protein activity, fatty acid biosynthesis, fatty acid degradation, peroxisome and glutathione metabolism and other functions or pathways. Conclusion There were lots of variable alternative splicing RNA in the hepatic tissues of alcoholic liver injury rats, suggested that the variable of these RNA might play an important role in the occurrence and development of alcoholic liver disease.