选择性雌激素受体调节剂对高糖血症大鼠胰腺组织氧化损伤等的影响  

EFFECT OF SELECTIVE ESTROGEN RECEPTOR MODULATORS ON OXIDATIVE INJURY OF PANCREATIC TISSUE IN RATS WITH HYPERGLYCEMIA

作　　者：张昊旻 乔炳龙[3] 李超[1] 齐卫红[1] 卢彩霞[1] 孙平 ZHANG Haomin;QIAO Binglong;LI Chao;QI Weihong;LU Caixia;SUN Ping(Department of Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao 266003, China)

机构地区：[1]青岛大学附属医院产科,山东青岛266003 [2]诸城市妇幼保健院产科 [3]青岛大学附属医院放射科 [4]青岛市第三人民医院产科

出　　处：《精准医学杂志》2021年第4期347-351,355,共6页Journal of Precision Medicine

基　　金：山东省医药卫生科技发展计划项目(2016WS0274)。

摘　　要：目的探讨选择性雌激素受体(ER)调节剂对高糖血症大鼠胰腺组织氧化损伤等的影响。方法将24只雌性SD大鼠随机分为对照组(A组)、高糖血症模型组(B组)、他莫昔芬(TAM)低剂量[2.5 mg/(kg·d)]处理组(C组)及TAM高剂量[5 mg/(kg·d)]处理组(D组),每组6只大鼠,利用RT-qPCR和Western Blot方法检测胰腺组织中ERα及铁死亡通路相关的谷胱甘肽过氧化物酶4(GPX4)、铁蛋白重链1(FTH1)、长链脂酰CoA合成酶4(ACSL4)mRNA和蛋白表达水平。采用生化方法检测大鼠胰腺组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-PX)的活性以及谷胱甘肽(GSH)、过氧化氢(H_(2)O_(2))、丙二醛(MDA)的含量。采用比色法检测胰腺组织中铁的含量。通过苏木精-伊红染色检测大鼠胰腺组织形态,并利用透射电子显微镜观察大鼠胰岛超微结构的变化。结果A~D组大鼠胰腺组织中ERα、GPX4、FTH1及ACSL4 mRNA和蛋白表达水平比较差异均有显著性(F=31.06~84.37,P<0.05);CAT、SOD、GSH-PX等酶活性以及GSH、H2O2、MDA、铁含量比较差异均有显著性(F=50.82~204.01,P<0.05)。B组大鼠胰腺组织出现明显的病理形态学改变,胰岛超微结构呈现明显的铁死亡特征;C、D组大鼠胰腺组织病理损伤得到有效缓解,同时,胰岛超微结构也趋于正常。结论选择性ER调节剂可能通过ER抑制胰腺组织氧化应激水平,降低细胞铁死亡,进而缓解高糖血症所致大鼠胰腺的病理损伤。Objective To investigate the effect of selective estrogen receptor(ER)modulators on oxidative injury of pancreatic tissue in rats with hyperglycemia.Methods A total of 24 female Sprague-Dawley rats were randomly divided into control group(group A),hyperglycemia model group(group B),low-dose[2.5 mg/(kg·d)]tamoxifen treatment group(group C),and high-dose[5 mg/(kg·d)]tamoxifen treatment group(group D),with 6 rats in each group.RT-qPCR and Western Blot were used to measure the mRNA and protein expression levels of ERαand the ferroptosis pathway-related genes glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1),and acyl-CoA synthetase long-chain family member 4(ACSL4)in pancreatic tissue.Biochemical methods were used to measure the activities of superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)and the content of glutathione(GSH),hydrogen peroxide(H_(2)O_(2)),and malondialdehyde(MDA)in pancreatic tissue.Colorimetry was used to measure the content of iron in pancreatic tissue.HE staining was used to observe the histomorphology of the pancreas,and a transmission electron microscope was used to observe the change in the ultrastructure of pancreatic islets.Results\There were significant differences in the mRNA and protein expression levels of ERα,GPX4,FTH1,and ACSL4 in pancreatic tissue between groups A,B,C,and D(F=31.06-84.37,P<0.05),and there were also significant differences in the activities of CAT,SOD,and GSH-PX and the content of GSH,H2O2,MDA,and iron between groups(F=50.82-204.01,P<0.05).Group B had marked pathomorphological changes of pancreatic tissue and features of ferroptosis in the ultrastructure of pancreatic islets,while groups C and D had effectively alleviated pathological injury of pancreatic tissue and a basically normal ultrastructure of pancreatic islets.Conclusion Selective ER modulators can inhibit oxidative stress and reduce ferroptosis in pancrea-tic tissue through ER,thus alleviating the pathological damage of the pancreas caused by hyperglycemia.

关 键 词：糖尿病 妊娠 糖尿病 实验性 雌激素受体Α 细胞死亡 铁 氧化性应激 超氧化物歧化酶 大鼠 Sprague-Dawley 

分 类 号：R714.256[医药卫生—妇产科学]