异欧前胡素对四氯化碳致小鼠急性肝损伤的保护作用  

Protective effects of isoimperatorin on CCl_4 induced acute liver injury in mice

作　　者：杨兴鑫 梁丽 王曦 董金材 李凤娇 顾雯[1,2] 俞捷 YANG Xing-xin;LIANG Li;WANG Xi;DONG Jin-cai;LI Feng-jiao;GU Wen;YU Jie(College of Pharmaceutical Science, Yunnan University of Traditional Chinese Medicine, Yunnan Kunming 650500, China;Kunming Key Laboratory for Metabolic Diseases Prevention and Treatment by Chinese Medicine, Yunnan Kunming 650500, China)

机构地区：[1]云南中医学院中药学院,云南昆明650500 [2]昆明市代谢性疾病中医药防治重点实验室,云南昆明650500

出　　处：《中国医院药学杂志》2018年第13期1358-1362,共5页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金(编号:81660596;81460623;81760733);云南省应用基础研究计划项目(编号:2017FF117-(013);2016FD050);云南省中青年学术和技术带头人后备人才(编号:2015HB053);云南省高校南药研究协同创新中心(编号:30270100500);云南省高层次中医药人才培养对象

摘　　要：目的:研究异欧前胡素对四氯化碳(CCl4)诱导的小鼠急性肝损伤的保护作用。方法:60只昆明种小鼠随机分为正常对照(生理盐水)组、模型(生理盐水)组、水飞蓟宾(阳性对照,16mg·kg^(-1))组和异欧前胡素低、中、高剂量(8,16,32mg·kg^(-1))组,连续灌胃给药7d,每天1次。末次给药1h后,除正常对照组外其余各组小鼠腹腔注射0.1%CCl4花生油溶液诱发小鼠急性肝损伤。16h后摘眼球取血并处死小鼠,测定肝脏指数,检测血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)及肝组织中丙二醛(MDA)、超氧化物歧化酶(SOD)及谷胱甘肽(GSH)水平;检测肝脏线粒体中MDA水平、ATP酶活性及线粒体膜电位。结果:CCl4诱导小鼠肝脏指数及血清ALT和AST水平显著升高,肝细胞肿胀、变性、坏死,出现明显炎性损伤;使肝组织及肝线粒体中MDA水平显著升高,SOD与GSH水平显著降低;同时导致肝线粒体中ATP酶活性显著降低,线粒体膜电位下降。而水飞蓟宾及异欧前胡素均可显著逆转CCl4引发的这些效应。结论:异欧前胡素对CCl4诱导的小鼠急性肝损伤具有保护作用,其机制可能与清除氧化应激产物MDA,增加细胞内抗氧化酶SOD与GSH活性及改善线粒体功能有关。OBJECTIVE To investigate the protective effects of isoimperatorin on acute liver injury induced by CCl4 in mice.METHODS A total of 60 mice were randomly divided into normal control group（normal saline）,model group（normal saline）,silybin group（positive control,16 mg·kg-1）and low dose,medium dose and high dose isoimperatorin groups（8,16 and 32 mg·kg-1）.Animals were intragastrically given corresponding compounds（or normal saline）once a day,totally for seven days.An hour after the last medication,acute liver injury model was induced by intraperitoneal injection of 0.1% CCl4（dissolved in arachisoil）in those groups except for normal control group.After sixteen hours,the eye balls of mice were removed to collect blood,and then the mice were sacrificed.The levels of alanine transarninase（ALT）and aspartate aminotransferase（AST）in serum and superoxide dismutase（SOD）,malondialdehyde（MDA）and glutathione（GSH）in liver tissues were detected.MDA level,ATPase activity and mitochondrial membrane potential in hepatic mitochondria were measured.RESULTS CCl4 resulted in the notable increase of liver indexes and ALT and AST levels in serum,the swelling,degeneration and necrosis of hepatic cells showing obvious inflammatory injury,the significant elevation of MDA level in the liver tissues and hepatic mitochondria,and the remarkable reduction of SOD and GSH levels.Moreover,the ATPase activity and mitochondrial membrane potential in hepatic mitochondria from the CCl4-damaged mice were significantly decreased.These effects induced by CCl4 were significantly inverted by silybin and isoimperatorin.CONCLUSION Isoimperatorin showed protective effects on CCl4 induced acute liver injury in mice.The action mechanism may be related to the elimination of oxidative stress product（MDA）and improvement of intracellular antioxidant enzyme activity（SOD and GSH）and mitochondrial function.

关 键 词：异欧前胡素 四氯化碳 肝损伤 保护作用 氧化应激 线粒体 

分 类 号：R96[医药卫生—药理学]