银杏叶提取物对二甲苯诱导肝损伤的影响  

Effects of Ginkgo Biloba Extract on Xylene-Induced Liver Injury

作　　者：米红梅[1] 张娜 王明慧 MI Hongmei;ZHANG Na;WANG Minghui(The Fourth People's Hospital of Hengshui,Hengshui,Hebei,China 053000;Maternal and Child Health Hospital of Hengshui,Hengshui,Hebei,China 053000)

机构地区：[1]河北省衡水市第四人民医院,河北衡水053000 [2]河北省衡水市妇幼保健院,河北衡水053000

出　　处：《中国药业》2025年第6期40-45,共6页China Pharmaceuticals

基　　金：河北省衡水市科技计划项目[2016014049Z]。

摘　　要：目的探讨银杏叶提取物(GBE)对二甲苯(XY)诱导肝损伤的影响及其作用机制。方法动物实验取雄性KM小鼠,随机分为对照组[等体积生理盐水(NS)]、模型组(等体积NS)、GBE组(50μg/mL),采用吸入法复制二甲苯中毒急性肝损伤小鼠模型,建模成功后腹腔注射给药或NS,每天1次,连续8周。细胞试验取AML 12细胞,设sh-NC+NS组(等体积NS)、sh-NC+GBE组(50μg/mL)、sh-KLF2+NS组(等体积NS)、sh-KLF2+GBE组(50μg/mL)。苏木精-伊红(HE)染色观察小鼠肝脏组织病理形态。采用酶联免疫吸附试验(ELISA)法检测肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)及白细胞介素6(IL-6)水平;流式细胞术检测活性氧(ROS)水平;Western blot法检测内皮型一氧化氮合酶/可溶性鸟苷酸环化酶(eNOS/sGC)通路相关蛋白;荧光定量聚合酶链式反应(qRT-PCR)法检测Kruppel样转录因子2(KLF2)的表达水平。结果与模型组比较,GBE组小鼠肝组织中炎性细胞浸润以及细胞损伤情况减少;GBE组小鼠肝组织中IL-1β、IL-6、TNF-α、ROS水平均显著降低(P<0.05),丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、丙二醛(MDA)水平显著降低,谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)及KLF2 mRNA水平显著升高(P<0.05)。与sh-NC+NS组比较,sh-NC+GBE组细胞中KLF2 mRNA水平显著升高,ROS水平显著降低;sh-KLF2+NS组细胞中KLF2 mRNA水平显著降低,IL-1β、IL-6、TNF-α蛋白表达水平显著升高(P<0.05);与sh-KLF2+NS组比较,sh-KLF2+GBE组细胞中KLF2 mRNA水平显著升高,IL-1β、IL-6、TNF-α表达水平显著降低(P<0.05)。结论GBE可用于改善二甲苯诱导的急性肝损伤,其机制可能为通过调节KLF2/eNOS/sGC信号轴抑制肝组织中氧化应激因子及炎性因子的表达。Objective To investigate the effects and underlying mechanisms of Ginkgo biloba extract(GBE)on xylene(XY)-induced liver injury.Methods In the animal experiment,male KM mice were randomly divided into a control group(NS,equal volume),a model group(NS,equal volume),and a GBE group(GBE solution,50μg/mL).An acute liver injury model was established via xylene inhalation.After successful modeling,the mice received intraperitoneal injections of the respective treatments once daily for eight weeks.In the cellular experiment,AML12 cells were assigned to the sh-NC+NS group(NS,equal volume),the sh-NC+GBE group(GBE solution,50μg/mL),the sh-KLF2+NS group(NS,equal volume),and the sh-KLF2+GBE group(GBE solution,50μg/mL).Hematoxylin-eosin(HE)staining and ELISA were performed to examine the pathological morphology of liver tissues.Enzyme-linked immunosorbent assay(ELISA)was used to detect inflammatory factors(tumor necrosisfactor-α,interleukin-1β,interleukin-6);reactive oxygen species(ROS)levels were assessed by flow cytometry;the expression of endothelial nitric oxide synthase/soluble guanylate cyclase(eNOS/sGC)pathway-related proteins was analyzed by western blot;and quantitative real-time PCR(qRT-PCR)was used to determine the expression levels of Kruppel-like factor 2(KLF2).Results The infiltration of inflammatory cells and cell damage of the mice's liver tissue in GBE group were reduced.Compared with the model group,the GBE group exhibited significantly reduced levels of IL-1β,IL-6,TNF-α,and ROS in liver tissues,as well as decreased levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and malondialdehyde(MDA),while glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),and KLF2 mRNA expression levels were significantly increased(P<0.05).Compared with the sh-NC+NS group,the sh-NC+GBE group showed a significant increase in KLF2 expression,whereas the sh-KLF2+NS group exhibited decreased KLF2 expression level and elevated IL-1β,IL-6,and TNF-αlevels(P<0.05).Compared with the sh-KLF2+NS group,the sh-K

关 键 词：银杏叶提取物 急性肝损伤 二甲苯 KLF2/eNOS/sGC信号通路 作用机制 小鼠 AML 12细胞 

分 类 号：R965[医药卫生—药理学] R285[医药卫生—药学]