摘要
目的基于代谢组学对对乙酰氨基酚(acetaminophen,APAP)诱导大鼠急性肝损伤的机制研究。方法24只Wistar大鼠随机分为正常对照组和APAP低(1 g·kg^-1)、中(2 g·kg^-1)、高(3 g·kg^-1)剂量组。造模后分别于6、24、48 h采血,48 h采血后取肝脏;测定血清谷氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平,并进行病理组织学观察。通过LC-MS技术检测血清样本,鉴定差异代谢物,分析代谢通路。结果与正常对照组比较,在24 h,中、高剂量组的ALT、AST水平有显著性差异(P<0.01);在48 h,低、中、高三组的ALT、AST水平均有显著性差异(P<0.05,P<0.01);且HE染色可见有不同程度的肝组织损伤。代谢组学结果显示,正常对照组与给药组的样本区分明显,共找出了45个差异代谢物,主要富集于甘油磷脂代谢、鞘脂代谢和初级胆汁酸的生物合成等代谢通路。结论对乙酰氨基酚致大鼠急性肝损伤可能与甘油磷脂代谢、鞘脂代谢,以及初级胆汁酸的生物合成等代谢通路有关。
Aim To study the mechanism of acetaminophen(APAP)-induced acute liver injury in rats based on metabolomics.Methods Twenty-four Wistar rats were randomly divided into normal control group and low-dose(1 g·kg^-1),middle-dose(2 g·kg^-1),and high-dose(3 g·kg^-1)APAP groups.Blood was collected 6,24,and 48 hours after modeling,and livers were collected after 48 hours.Serum glutamate aminotransferase(ALT)and aspartate aminotransferase(AST)levels were measured and pathologically observed.LC-MS technology was used to detect serum samples,identify differential metabolites,and analyze metabolic pathways.Results Compared with normal control group,the levels of ALT and AST in medium and high dose groups were significantly different at 24 hours(P<0.05,P<0.01);at 48 hours,low,middle and high groups were significantly different(P<0.05,P<0.01);HE staining showed different degrees of liver tissue damage.Metabolomics results showed that the samples in control group and administration group were clearly distinguished.A total of 45 differential metabolites were found,which were mainly concentrated in metabolic pathways such as glycerophospholipid metabolism,sphingolipid metabolism,and primary bile acid biosynthesis.Conclusions APAP-induced acute liver injury in rats may be related to metabolic pathways such as glycerophospholipid metabolism,sphingolipid metabolism,and primary bile acid biosynthesis.
作者
李修龙
胡诚
李云鹤
杨蓉
陈龙
贾益群
LI Xiu-long;HU Cheng;LI Yun-he;YANG Rong;CHEN Long;JIA Yi-Qun(Dept of Analysis & Testing, Science and Technology Experiment Center,Shanghai University of Taditional Chinese Medcine,Shanghai 201203,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2020年第8期1068-1075,共8页
Chinese Pharmacological Bulletin
基金
上海市教委预算内项目(No 18LK022)
上海市卫生健康委员会科研项目(No 201740166)
虹口区卫生健康委员会“国医强优”专项课题(No HGY-MGB-2018-01-08)
上海中医药大学预算内项目(No A1-GY0303)。
