大蒜素分解产物二烯丙基二硫对小鼠急性肝损伤的保护作用

Protective effects of decomposition product diallyl disulfide of allicin on acute liver injury in mice

中文关键词:  大蒜  二烯丙基二硫  肝损伤  转录组学  肠道菌群

英文关键词:garlic  diallyl disulfide  liver injury  transcriptomics  gut microbiota

中文摘要:

      目的 研究大蒜活性物质二烯丙基二硫(diallyl disulfide, DADS)对四氯化碳诱导的小鼠急性肝损伤的保护作用及其机制。方法 将36只Balb/c小鼠随机分为4组, 分别为正常组、模型组、阳性组和DADS组。测定小鼠体质量与肝脏指数、天门冬氨酸氨基转移酶(aspartate aminotransferase, AST)、碱性磷酸酶(alkaline phosphatase, ALP)、总超氧化物歧化酶(superoxide dismutase, SOD)、丙二醛(malonaldehyde, MDA)水平, 观察肝脏病理学变化; 将肝脏样品进行转录组测序, 确定差异基因行使的主要生物学功能; 将盲肠内容物进行16S rRNA测序, 在各个分类水平上进行群落结构的统计分析。结果 DADS可以显著降低四氯化碳肝损伤小鼠肝脏指数, 降低AST、ALP活力, 提高SOD活力; 减少肝脏组织损伤面积、细胞坏死、炎细胞浸润; 转录组学分析显示有130个差异表达基因, 基因本体论联合会建立的数据库(gene ontology, GO)富集分析显示这些差异基因主要涉及类固醇代谢过程、脂质代谢过程、胆固醇代谢过程, 京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes, KEGG)富集分析显示这些差异基因主要涉及类固醇生物合成、视黄醇代谢、药物代谢-细胞色素P450和胆汁分泌等通路。16S rRNA测序结果显示, DADS处理增加了肝损伤小鼠的厚壁菌门、norank_f_Muribaculaceae、Lachnospiraceae_NK4A136_group的相对丰度, 降低了变形菌门、Escherichia-Shigella的相对丰度。结论 DADS具有较强的抗四氯化碳肝损伤的潜力, 其机制可能是通过提高体内抗氧化水平、调控类固醇代谢相关基因、调节胆汁酸代谢和肠道菌群组成。

英文摘要:

      Objective To investigate the protective effects and mechanism of garlic active substance diallyl disulfide (DADS) on carbon tetrachloride induced acute liver injury in mice. Methods Thirty-six Balb/c mice were randomly divided into 4 groups: Control group, model group, positive group and DADS group. The body weight and liver index, aspartate aminotransferase (AST), alkaline phosphatase (ALP), superoxide dismutase (SOD) and malondialdehyde (MDA) levels of mice were determined, and the pathological changes of liver were observed. Transcriptome sequencing was performed on liver samples to determine the main biological functions performed by differential genes. The cecum content was sequenced by 16S rRNA, and the community structure was statistically analyzed at each taxonomic level. Results DADS significantly reduced liver index, decreased AST and ALP activity, increased SOD activity in mice with carbon tetrachloride liver injury; reduced the area of liver tissue damage, cell necrosis, and inflammatory cell infiltration; totally 130 differentially expressed genes were identified. Gene ontology (GO) enrichment analysis showed that these differentially expressed genes were mainly related to steroid metabolic process, lipid metabolic process, and cholesterol metabolic process. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that these differentially expressed genes were mainly involved in steroid biosynthesis, retinol metabolism, drug metabolism-cytochrome P450 and bile secretion. 16S rRNA sequencing showed that DADS treatment increased the relative abundance of Firmicutes, norank_f_Muribaculaceae and Lachnospiraceae_NK4A136_group in mice with liver injury, and decreased the relative abundance of Proteobacteria and Escherichia-Shigella. Conclusions DADS has a strong potential against carbon tetrachloride liver injury, probably by increasing antioxidant levels in vivo, regulating steroid metabolism-related genes, modulating bile acid metabolism and gut microbiota composition.