应用基因芯片技术分析甘草酸改善大鼠酒精性肝损伤的作用机制  

Analysis of the improvement mechanism of glycyrrhizic acid on alcoholic liver injury rats by gene chip technology

作　　者：从美丽[1] 古丽拉莱·多力坤 周蓓[1] 王忠[1] 吕晓敏[1] CONG Mei-li;Gulilalai·Duolikun;ZHOU Bei;WANG Zhong;LYU Xiao-min(Xinjiang Medical University Animal Laboratory Center,Urumqi 830011,China)

机构地区：[1]新疆医科大学动物实验中心,乌鲁木齐830011

出　　处：《医学动物防制》2022年第4期374-378,共5页Journal of Medical Pest Control

基　　金：新疆维吾尔自治区自然科学基金联合基金项目(2021D01C247)。

摘　　要：目的运用基因芯片技术检测甘草酸对大鼠酒精性肝损伤保护作用的分子机制。方法 45只大鼠随机分为3组:模型组、甘草酸组、正常对照组,连续灌服56度白酒8周,处理动物,测定血清谷丙转氨酶(ALT)和谷草转氨酶(AST)水平;抽提肝脏RNA,全基因组表达谱芯片检测,运用GO和KEGG Pathway富集分析。结果与正常对照组比较,模型组血清AST和ALT含量显著升高,差异有统计学意义(t=7.784,P<0.05;t=11.366,P<0.05),肝组织出现显著的肝损伤;与模型组相比,甘草酸组能显著改善肝组织病变,降低血清AST和ALT含量,差异有统计学意义(t=6.448,P<0.05;t=7.526,P<0.05)。芯片结果分析显示,甘草酸组与模型组共筛选出7 482条差异可变剪切RNA(Splicing Index<-3或>3,P<0.05),其中差异可变剪切编码RNA为6 512条。对差异可变剪切编码RNA进行GO和Pathway富集分析,结果显示,主要与乙醇分解代谢、肝星状细胞活化、氧化还原酶活性、氨基酸合成代谢、脂肪酸的生物合成、Notch信号通路等功能或通路有关。结论甘草酸在改善大鼠酒精性肝损伤病变过程中存在大量差异可变剪切编码RNA,提示甘草酸可通过调节多基因可变剪切改善酒精性肝损伤病变。Objective To investigate the molecular mechanism of glycyrrhizic acid on the protection of alcoholic liver injury in rats using gene microarray technology.Methods Forty-five rats were randomly divided into three groups: normal control group, model group and glycyrrhizic acid group.A rat model of alcoholic liver injury was established by gavage of 56-degree spirit distilled liquor.After eight weeks of continuous intragastric administration, serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels were measured.The liver RNA was extracted, detected using a whole-genome expression profiling microarray, and analyzed for enrichment using GO and KEGG Pathway.Results Compared with the normal control group, the serum AST and ALT levels in the model group were significantly increased, and the differences were statistically significant(t=7.784,P<0.05;t=11.366,P<0.05),and the liver tissue showed significant liver damage.Compared with the model group, the glycyrrhizic acid group could significantly improve the liver tissue lesions and reduce the serum AST and ALT contents and the difference was statistically significant(t=6.448,P<0.05;t=7.526,P<0.05).The microarray analysis showed: a total of 7 482 differentially alternative splicing RNA(Splicing Index<-3 or >3,P<0.05) were screened in the glycyrrhizic acid and model groups, of which 6 512 were differentially alternative splicing coding RNA.GO and KEGG Pathway enrichment analysis of differentially alternative splicing coding RNA showed that it was mainly related to functions or Pathways such as ethanol catabolic process, hepatic stellate cell activation, oxidoreductase activity, amino acid anabolism, fatty acid biosynthesis, Notch signaling pathway.Conclusion There are lots of variable alternative splicing RNA in the progress of improving alcoholic liver injury in rats suggests that glycyrrhizic acid can improve alcoholic liver injury by regulating polygenic alternative splicing RNA.

关 键 词：基因芯片 酒精性肝损伤 甘草酸 可变剪切 GO富集分析 KEGG Pathway富集分析 

分 类 号：R-332[医药卫生] R575.5