血人参乙酸乙酯部位对APAP诱导小鼠急性肝损伤的保护作用  

Protective Effect of Acetic Ether Extraction of the Alcoholic Extract of Roots of Indigofera stachyoides on the Acute Liver Injury Induced by APAP in Mice

作　　者：杨宇莎 时京珍[2] 雷钟 周威 梁妍 刘杰[3] 郝小燕 杨虹[2] YANG Yu-sha;SHI Jing-zhen;LEI Zhong;ZHOU Wei;LIANG YanI;LIU Jie;HAO Xiao-yan;YANG Hong(School of Pharmacy,Guizhou Medical University,Guiyang 550004,China;Department of Basic Medical Sciences,Guiyang University of Chinese Medicine,Guiyang 550025,China;Key Laboratory of Basic Pharmacology of Ministry of Education,Zunyi Medical University,Zunyi Guizhou 563099,China)

机构地区：[1]贵州医科大学药学院,贵州贵阳550004 [2]贵阳中医学院基础医学院,贵州贵阳550025 [3]遵义医学院基础药理省部共建教育部重点实验室,贵州遵义563099

出　　处：《时珍国医国药》2018年第4期786-789,共4页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(81460640);贵州省科技合作计划项目(黔科合LH字[2016]7122号);贵州省科学技术基金项目(黔科号ZY字[2013]3006号)

摘　　要：目的研究血人参乙酸乙酯部位对对乙酰氨基酚(Acetaminophen,APAP)诱导小鼠急性肝损伤的保护作用。方法将雄性KM小鼠随机分为正常对照组、模型组、双环醇组、血人参乙酸乙酯部位低、高剂量组,每组10只,双环醇组连续灌胃给予双环醇(150 mg·kg^(-1))4天。血人参乙酸乙酯部位低、高剂量组分别皮下注射血人参乙酸乙酯(200mg·kg^(-1),400 mg·kg^(-1)),连续4天,末次给药8 h后,除正常对照组以外,其余各组均腹腔注射300 mg·kg^(-1)对乙酰氨基酚水溶液建立小鼠急性肝损伤模型,禁食,16 h后,断头取血并分离血清,解剖取肝脏。测定小鼠血清中丙氨酸氨基转氨酶(ALT)、天冬氨酸转氨酶(AST),观察肝组织病理学的变化情况,Realtime RT-PCR检测肝组织Cyp1a2,Cyp2e1和Cyp3a11以及Egr-1、TNF-α基因的表达水平。结果血人参乙酸乙酯部位低、高剂量组未对正常小鼠造成明显肝损伤且能降低APAP模型小鼠血清中ALT、AST含量并明显改善肝细胞坏死病变的程度,抑制肝组织Cyp1a2,Cyp2e1和Cyp3a11以及Egr-1、TNF-α基因的表达水平。结论血人参乙酸乙酯部位未见明显肝毒性且具有较好的肝脏保护效果,可能与其抑制Cyp1a2,Cyp2e1和Cyp3a11代谢酶表达,下调Egr-1和TNF-α基因表达有关。Objective To study the protective effect of ethyl acetate on the acute liver injury induced by acetaminophen（APAP）in mice. Methods KM mice were randomly divided into normal control group,model group,bicyclol group,low level of ethyl acetate group and 10 mice in each group. The bicyclol group was given bicyclol（150 mg · kg^-1） 4 days.（200 mg · kg^-1,400 mg · kg^-1） were injected subcutaneously into the low and high dose groups for 4 days. After 8 hours of the last administration,the mice in the normal control group The mice in the other groups were injected intraperitoneally with 300 mg · kg^-1 acetaminophen aqueous solution to establish acute liver injury model. Fasting for 16 hours,the mice were sacrificed and the serum was separated and the liver was dissected. The levels of alanine aminotransferase（ALT） and aspartate aminotransferase（AST） in serum were measured and the pathological changes of liver were observed. Real time RT-PCR was used to detect the expression of Cyp1a2,Cyp2e1 and Cyp3a11 and Egr-1,TNF-α gene expression levels. Results The levels of ALT and AST in the serum of APAP mice were significantly decreased and the levels of hepatocellular necrosis were significantly improved in the low and high dose groups,and the liver tissues Cyp1a2,Cyp2e1 and Cyp3a11 and Egr-1,TNF-α gene expression levels. Conclusion-There is no obvious hepatotoxicity in the ethyl acetate fraction of blood ginseng and has a good protective effect on the liver,which may be related to its inhibition of the expression of Cyp1a2,Cyp2e1 and Cyp3a11 metabolic enzymes,down-regulation of Egr-1 and TNF-α gene expression.

关 键 词：血人参 药物性肝损伤 对乙酰氨基酚 EGR-1 TNF-α P450酶 

分 类 号：R285.5[医药卫生—中药学]