Fisetin对缺血再灌注肝脏氧化应激性损伤的保护作用  

Protective Effects of Fisetin on Oxidative Stress Injury Induced by Hepatic Ischemia-reperfusion

作　　者：李泽信[1] 王霄[2] 王迎[1] 张妤 李荣[4] 王建国[1] LI Zexin;WANG Xiao;WANG Ying;ZHANG Yu;LI Rong;WANG Jianguo(Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Xinxiang Medical College, Weihui Henan 453100, China;School of Pharmacy, Xinxiang Medical College, Xinxiang Henan 453003,China;Department of Neurology, Anyang People’s Hospital, Anyang Henan 455000,China;School of Nursing, Xinxiang Medical College, Xinxiang Henan 453003,China)

机构地区：[1]新乡医学院第一附属医院肝胆胰外科,河南卫辉453100 [2]新乡医学院药学院,河南新乡453003 [3]安阳市人民医院神经内科,河南安阳455000 [4]新乡医学院护理学院,河南新乡453003

出　　处：《河南医学高等专科学校学报》2021年第1期1-5,共5页Journal of Henan Medical College

基　　金：新乡医学院第一附属医院青年基金资助项目(QN-2017-B001);河南省医学科技攻关联合共建项目(LHGJ20200495)。

摘　　要：目的探讨3,3′4′7-四羟基黄酮(Fisetin)减轻缺血再灌注(ischemia/reperfusion,I/R)肝脏氧化应激性损伤的作用及可能机制。方法18只C57BL/6雄性小鼠随机分为Sham组、I/R组和I/R+Fisetin组,各6只。I/R组和I/R+Fisetin组小鼠建立肝脏I/R模型,Sham组仅进行开关腹手术。I/R+Fisetin组小鼠经腹腔注射Fisetin 50 mg·kg-1提前1 h预处理;Sham组和I/R组小鼠术前不进行药物干预。检测3组小鼠血清中谷丙转氨酶(ALT)和谷草转氨酶(AST)水平;苏木精-伊红(HE)染色观察3组小鼠肝脏组织病理学变化;2′,7′-二氯荧光黄双乙酸盐(2,7-dichlorodi-hydrofluorescein diacetate,DCFH-DA)荧光探针法检测3组小鼠肝脏细胞活性氧自由基(reactive oxygen species,ROS)水平;试剂盒检测3组小鼠肝脏组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性。结果小鼠肝脏再灌注6 h后,I/R+Fisetin组小鼠ALT、AST水平较I/R组下降[(108.85±25.73)IU·L^(-1) vs(213.45±49.51)IU·L^(-1);(194.72±45.32)IU·L^(-1) vs(422.55±99.30)IU·L^(-1)],差异有统计学意义(P<0.05)。I/R+Fisetin组小鼠肝脏组织内中性粒细胞浸润和肝脏坏死面积明显减少。I/R+Fisetin组肝脏组织细胞ROS水平(74158±17035)RFU·mgprot^(-1),低于I/R组(153096±35287)RFU·mgprot^(-1),差异有统计学意义(P<0.05)。I/R+Fisetin组小鼠肝脏组织MDA含量(6.287±1.444)nmol·mgprot^(-1),低于I/R组(12.781±3.086)nmol·mgprot^(-1),差异有统计学意义(P<0.05)。I/R+Fisetin组小鼠肝脏组织SOD和GSH-Px活性均较I/R组增加,差异有统计学意义(P<0.05)。结论Fisetin对I/R肝脏氧化应激性损伤的保护作用可能是通过诱导SOD、GSH-Px活性增加,降低ROS水平和MDA含量实现的。Objective To investigate the effect and possible mechanism of 3,3′4′7-tetrahydroxyflavone(Fisetin)in reducing liver oxidative stress injury induced by ischemia-reperfusion.Methods Eighteen C57BL/6 male mice were randomly divided into 3 groups:Sham group,I/R group and I/R+Fisetin group,with 6 mice in each group.Liver I/R model was established in I/R group and I/R+Fisetin group,and abdominal switching surgery was performed only in Sham group.Mice in the I/R+Fisetin group were pretreated by intraperitoneal injection of Fisetin 50 mg·kg-1 at 1 h before modeling;mice in the Sham group and I/R group were not treated with medication before surgery.The levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in the serum of the 3 groups of mice were detected;Hematoxylin-eosin(HE)staining was performed to observe the pathological changes of the liver tissues of the 3 groups of mice;the levels of reactive oxygen species(ROS)of hepatocyte in 3 group were detected by dichlorodi-hydrofluorescein diacetate;The contents of malondialdehyde(MDA),the active superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in liver tissues of mice were measured by sensitive testing kits.Results Six hours after mouse liver reperfusion,the levels of ALT and AST of mice in I/R+Fisetin group were lower than those in I/R group[(108.85±25.73)IU·L^(-1) vs(213.45±49.51)IU·L^(-1);(194.72±45.32)IU·L^(-1) vs(422.55±99.30)IU·L^(-1)],the differences were statistically significant(P<0.05);Neutrophil infiltration and necrotic area of liver tissues were both remarkably reduced in I/R+Fisetin group.The level of hepatocyte ROS was(74158±17035)RFU·mgprot^(-1) in I/R+Fisetin group,lower than that in I/R group(153096±35287)RFU·mgprot^(-1),and the difference were statistically significant(P<0.05).The content of MDA was(6.287±1.444)nmol·mgprot^(-1) in I/R+Fisetin group,lower than that in I/R group(12.781±3.086)nmol·mgprot^(-1),and the difference was statistically significant(P<0.05).The activities of SOD and GSH-Px of liver

关 键 词：肝脏缺血再灌注损伤 3 3′4′7-四羟基黄酮 活性氧自由基 氧化应激性损伤 大鼠 

分 类 号：R-332[医药卫生]