基于蛋白质组学分析栀子水提液肝损伤时-毒关系及其机制

研究栀子水提液致大鼠肝毒性的时-毒关系及其作用机制.大鼠随机分为C组(0 d),D5组(5 d),D12组(12 d),D19组(19 d),D26组(给药19 d停药7d).各组灌胃给予对应时长栀子水提物,给药剂量为10 g,kg-1,C组给予等量生理盐水.各组末次给药后麻醉大鼠,摘取肝脏,苏木精-伊红(hemato...

Study on time-toxicity relationship and mechanism of Gardeniae Fructus extract on hepatoxicity in rats based on proteomics

To study the time-toxicity relationship and mechanism of Gardeniae Fructus extract on the hepatoxicity in rats.Rats were randomly divided into C group(0 day),D5 group(5 days),D12 group(12 days),D19 group(19 days),and D26 group(7 days recovery after 19 days of administration).The rats in normal group received normal saline through intragastric administration,and the rats in other groups received 10 g·kg^-1Gardeniae Fructus extract through intragastric administration.After the final administration,the livers were collected.Hematoxylin-eosin staining was used to observe the histopathological changes in the liver tissue.Total liver proteins were extracted for proteomic analysis,detected by the Nano-ESI liquid-mass spectrometry system and identified by Protein Disco-very software.SIEVE software was used for relative quantitative and qualitative analysis of proteins.The protein-protein interaction network was constructed based on STRING.Cytoscape software was used for cluster analysis of differential proteins.Kyoto encyclopedia of genes and genomes(KEGG)database was used to perform enrichment signal pathway analysis.Pearson correlation analysis was performed for the screened differential protein expression and liver pathology degree score.The results showed that the severity of liver injury in D5,D12 and D19 groups was significantly higher than that in group C.The degree of liver damage in D5 group was slightly higher than that in D12 and D19 groups,with no significant difference between group D26 and group C.Totally 147 key differential proteins have been screened out by proteomics and mainly formed 6 clusters,involving in drug metabolism pathways,retinol metabolism pathways,proteasomes,amino acid biosynthesis pathways,and glycolysis/gluconeogenesis pathways.The results of Pearson correlation analysis indicated that differential protein expressions had a certain temporal relationship with the change of liver pathological degree.The above results indicated that the severity of liver damage caused by Gardeniae Fructus extract did not increase with time and would recover after drug with drawal.The above pathways may be related to the mechanism of liver injury induced by Gardeniae Fructus extract.