京大戟醋制改善肠道菌群紊乱降低肠毒性作用研究

Vinegar-processed Euphorbiae Pekinensis Radix improves intestinal flora disorder and reduces colon toxicity

为研究京大戟醋制前后对肠道菌群结构的影响,探索京大戟醋制减毒的作用机制。该研究考察了不同溶剂对京大戟中Casbane型二萜的提取效果,筛选出最佳溶剂富集该类成分。将京大戟醋制前后二萜富集部位灌胃给药14 d后,采用16S核糖体RNA基因(16S rDNA)测序技术检测肠道菌群结构变化,并结合肠道病理损伤结果,通过相关性分析,筛选与京大戟醋制降低肠毒性相关的菌群。研究结果显示,以氯仿为提取溶剂,采用索式提取的方法能够较好地富集京大戟中的Casbane型二萜。16S rDNA测序结果显示,京大戟灌胃给药后肠道菌群结构发生显著变化,醋制后能够逆转这一改变,部分候选菌群可能与醋制减毒相关。进一步通过对候选菌群与肠黏膜损伤相关指标的相关性分析,发现与生品组相比,京大戟醋制后能够下调部分致病菌如黏液杆菌属、嗜胆菌属、瘤胃梭菌属等菌属的丰度,同时上调部分益生菌如肠杆菌属、瘤胃科;CG-014、巴恩斯菌属、分节丝状菌属等菌属的丰度。该研究表明京大戟导致的肠道毒性反应可能与其导致肠道菌群的紊乱相关,醋制后通过上调益生菌并下调致病菌的丰度改善肠道菌群的紊乱,重塑肠道黏膜屏障功能,从而使得毒性降低。

The present study investigated the effect of Euphorbiae Pekinensis Radix(EPR)on intestinal flora structure before and after vinegar processing and explored the detoxification mechanism of vinegar-processed EPR.In this study,the extraction efficiency of casbane diterpenes from EPR with different solvents was investigated,and the optimal solvent was selected to enrich these components.After 14 days of intragastric administration of total diterpene extract of EPR and vinegar-processed EPR,16 S rDNA sequencing technology was used to detect the structural changes of intestinal flora.The flora related to the intestinal toxicity of EPR was screened out based on the results of intestinal pathological damage by correlation analysis.The results showed that Soxhlet extraction with chloroform as extraction solvent could enrich Casbane diterpenes in EPR.As revealed by 16 S rDNA sequencing results,EPR could significantly change the structure of intestinal flora,which could be reversed by vinegar-processing EPR.Some intestinal flora candidates might be related to detoxification of vinegar processing.The correlation analysis of intestinal flora candidates and indexes related to intestinal mucosal injury showed that compared with EPR,vinegar-processed EPR could down-regulate the abundance of some pathogenic bacteria such as Mucispirillum,Bilophila,and Ruminiclostridium,and up-regulated some probiotics such as Enterorhabdus,Ruminococcaceae;CG-014,Barnesiella,and Candidatus.The intestinal toxicity caused by EPR may be related to the disturbance of intestinal flora,and vinegar-processed EPR can improve intestinal flora disorder by up-regulating the abundance of probiotics and down-regulating the abundance of pathogenic bacteria to remodel the intestinal mucosal barrier and reduce toxicity.