银杏酸诱导铁死亡发挥抗肝纤维化效应的大鼠实验研究  

Study on anti-hepatic fibrosis effect of ferroptosis induced by ginkgoic acid in rats

作　　者：郝文娟 张赛 夏童 刘考[1] HAO Wen-juan;ZHANG Sai;XIA Tong;LIU Kao(Department of Organ Transplantation,Qilu Hospital of Shandong University,Jinan 250012,China)

机构地区：[1]山东大学齐鲁医院器官移植科,山东济南250012

出　　处：《中国现代普通外科进展》2025年第2期103-107,共5页Chinese Journal of Current Advances in General Surgery

基　　金：山东省自然科学基金项目(ZR2023QH280)。

摘　　要：目的:基于大鼠肝纤维化模型探讨银杏酸(GA)抗肝纤维化效应及机制。方法:分别利用四氯化碳(CCl_(4))及硫代乙酰胺(TAA)构建大鼠肝纤维化模型,给予GA或联合铁死亡抑制剂Ferrostatin-1(Fer-1)干预,获取大鼠肝组织,分别给予HE染色、Masson染色、天狼猩红染色后行病理组织学评估;酶联免疫吸附测定(ELISA)检测外周血中肝纤维化标志物透明质酸酶(HA)、层粘连蛋白(LN)、Ⅳ型胶原(Ⅳ-C)、Ⅲ型前胶原(PC-Ⅲ)表达水平。Western blot检测铁死亡标志物谷胱甘肽过氧化物酶4(GPX4)、铁蛋白重链1(FTH1)蛋白表达水平。结果:HE染色结果显示,与TAA组及CCl_(4)组相比,GA组大鼠肝纤维化病理学改变显著减轻;Masoon及天狼猩红染色结果显示,与TAA组及CCl_(4)组相比,GA组大鼠肝脏组织中胶原纤维比例均显著下降(P<0.05);ELISA结果显示,与TAA组及CCl_(4)组相比,GA组大鼠外周血中HA、LN、Ⅳ-C、PC-Ⅲ水平均显著下降(P<0.05)。给予肝纤维化大鼠GA联合Ferrostatin-1(Fer-1)干预后,GA组大鼠肝脏中GPX4、FTH1表达水平较TAA组、CCl_(4)组显著上升(P<0.05),Fer组大鼠肝脏GPX4、FTH1水平较GA组显著下降(P<0.05);组织病理学结果显示,Fer组大鼠肝胶原组织比例较GA组显著上升(P<0.05)。结论:GA具有抗肝纤维化效应,且与诱导铁死亡相关。Objective:To investigate the effect and mechanism of ginkgo acid(GA)on hepatic fibrosis in rats.Methods:CCl_(4) and TAA were used to construct rat liver fibrosis model,and GA or combined ferroptosis inhibitor(Fer-1)was given to intervene.The liver tissue and serum of rats were obtained and histopathologically evaluated by HE,Masson and Sirius red staining,respecively.The expression of HA,LN,Ⅳ-C and PC-Ⅲ in serum were detected by Elisa and the expression of GPX4 and FTH1 were detected by Western blot.Results:HE staining showed that,compared with TAA and CCl_(4) groups,the fibrosis level of GA group was significantly decreased.The results of Masoon and Sirius red staining showed that compared with TAA and CCl_(4) groups,the rate of collagen fibers in liver of GA group was significantly decreased(P<0.05).Elisa results showed that compared with TAA and CCl_(4) groups,the levels of HA,LN,Ⅳ-C and PC-Ⅲ in serum of rats in GA group were significantly decreased(P<0.05).After the intervention of GA combined with Fer-1,Western blot results showed that compared with TAA and CCl_(4) groups,the expression of GPX4 and FTH1 in liver of rats in GA group were significantly increased(P<0.05).Compared with GA group,GPX4 and FTH1 levels in Fer group were significantly decreased(P<0.05);The histopathological results showed that compared with GA group,the rate of liver collagen fibers in Fer group was significantly increased(P<0.05).Conclusion:GA has anti-hepatic fibrosis effect,which is associated with inducing ferroptosis.

关 键 词：肝纤维化 银杏酸 铁死亡 大鼠 

分 类 号：R575[医药卫生—消化系统]