去铁胺对糖尿病大鼠肝细胞铁死亡通路的影响  

Effect of ferroamine on the ferroptotic cell death pathway in hepatocytes of diabetic rats

作　　者：杨文曲[1] 韩冲芳[1] 贺建东[1] 王慧[1] 李浩甲 YANG Wenqu;HAN Chongfang;HE Jiandong;WANG Hui;LI Haojia(Department of Anesthesiology,Third Hospital of Shanxi Medical University,Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Tongji Shanxi Hospital,Taiyuan 030032,China;College of Anesthesiology,Shanxi Medical University)

机构地区：[1]山西医科大学第三医院,山西白求恩医院,山西医学科学院,同济山西医院麻醉科,太原030032 [2]山西医科大学麻醉学院麻醉教研室

出　　处：《山西医科大学学报》2023年第2期203-207,共5页Journal of Shanxi Medical University

基　　金：山西省应用基础研究项目(201601D011121)。

摘　　要：目的评价去铁胺对糖尿病大鼠肝细胞铁死亡通路的影响。方法健康雄性SD大鼠,体质量240~290 g,采用随机数字表法分为3组(n=12):正常组(Con组)、糖尿病组(DM组)和去铁胺处理组(DFO组)。DM组和DFO组采用腹腔注射链脲佐菌素(STZ)55 mg/kg制备糖尿病大鼠模型。DFO组在造模后第24天开始每日腹腔注射去铁胺(0.2 mg/g)持续1周。观察各组在造模后第1,3,10,17,24,31天的体质量、血糖值、24 h饮水量的变化。造模后第31天断尾取血,血液生化仪测血浆丙氨酸氨基转移酶(ALT)浓度。取血后处死大鼠,取肝组织,HE染色观察肝脏的病理学变化,普鲁士蓝染色观察肝细胞内含铁小粒数量;Western blot法测定肝细胞微管相关蛋白3Ⅱ(LC3Ⅱ)、铁蛋白重链(FTH)和核受体共同激活因子4(NCOA4)的表达。结果与Con组比较,DM组和DFO组造模后第3,10,17,24,31天血糖和饮水量明显升高(P<0.05),造模后第17,24,31天体质量明显降低(P<0.05);与DM组比较,DFO组造模后饮水量和体质量差异均无统计学意义(P>0.05),造模后第1,3,10,17,24天血糖无统计学差异,第31天血糖明显降低(P<0.05)。造模后第31天,与Con组相比,DM组和DFO组ALT、FTH、NCOA4、LC3Ⅱ均升高(P<0.05),肝细胞肿胀,含铁小粒数量明显增多;与DM组相比,DFO组ALT、FTH、NCOA4、LC3Ⅱ均下降(P<0.05),肝细胞结构较完整,含铁小粒数目明显减少。结论去铁胺减轻糖尿病大鼠肝细胞损伤可能与抑制铁死亡通路中的肝细胞内NCOA4的表达有关。Objective To evaluate the effect of ferroamine on the ferroptotic cell death pathway in hepatocytes of diabetic rats.Methods Healthy Sprague-Dawley rats,weighing 240~290 g,were randomly divided into 3 groups(n=12):control group(Con group),diabetic group(DM group),and ferroamine group(DFO group).The diabetic model was induced by intraperitoneal injection of 55 mg/kg streptozotocin(STZ)in DM group and DFO group.The rats were intraperitoneally injected with 0.2 mg/kg ferroamine once a day from the 24th day after modelling for one week in DFO group.Body weight,blood sugar level and 24-hour water intake were recorded in each group at day 1,3,10,17,24,31 after modelling.The blood was taken by cutting off the tails of rats at day 31 after modelling to measure the level of plasma alanine aminotransferase(ALT)by blood biochemical analyzer.Then rats were sacrificed and the hepatic tissues were obtained to detect the pathological changes of the liver by HE staining and the number of iron particles in cells by perls staining.The expression of microtubule-associated protein 3Ⅱ(LC3Ⅱ),ferritin heavy chain(FTH),and nuclear receptor coactivator 4(NCOA4)in hepatocytes was determined by Western blot.Results Compared with Con group,the blood sugar and the 24-hour water intake were increased at day 3,10,17,24,31 after modelling in DM group and DFO group(P<0.05),while the body weight was decreased at day 10,17,24,31 after modelling(P<0.05).Compared with DM group,the 24-hour water intake and the body weight showed no significant difference at each time point in DFO group(P>0.05),and the blood sugar had no significant difference at day 1,3,10,17,24 after modelling(P>0.05),while the blood sugar was decreased at day 31 after modelling(P<0.05).At day 31 after modelling,compared with Con group,the plasma level of ALT and the expression of FTH,NCOA4,and LC3Ⅱwere upregulated in DM group and DFO group(P<0.05),and the liver cells were swollen and the number of iron particles was significantly increased.Compared with DM group,the plasma le

关 键 词：去铁胺 糖尿病 铁死亡 核受体共同激活因子4 

分 类 号：R587.1[医药卫生—内分泌]