柚皮素调控SIRT1/PGC-1α通路对妊娠期糖尿病模型大鼠糖脂代谢和氧化应激的影响  

Effects of naringenin on glucose and lipid metabolism and oxidative stress in rats with gestational diabetes by regulating the SIRT1/PGC-1αpathway

作　　者：布兰娜 郝月梅 李晓敬[1] 乔素兰[1] 王光祖 吴素静[1] 姚春霞[2] Bu Lanna;Hao Yuemei;Li Xiaojing;Qiao Sulan;Wang Guangzu;Wu Sujing;Yao Chunxia(Department of Neonatology,Handan Maternal and Child Health Hospital&Handan Children’s Hospital,Handan 056000,China;School of Medical,Hebei University of Engineering,Handan 056038,China)

机构地区：[1]邯郸市妇幼保健院,邯郸市儿童医院新生儿科,邯郸056000 [2]河北工程大学医学院,邯郸056038

出　　处：《中华内分泌外科杂志（中英文）》2024年第6期794-800,共7页Chinese Journal of Endocrine Surgery

基　　金：河北省自然科学基金(H2020402004);邯郸市科学技术研究与发展计划项目(19422083040ZC)。

摘　　要：目的探究柚皮素(NAR)对妊娠期糖尿病(GDM)大鼠糖脂代谢和氧化应激的影响与机制。方法取10只正常妊娠大鼠为对照组(control组),采用一次性尾静脉注射链脲佐菌素(STZ,35 mg/kg)制备GDM模型,将造模成功的50只大鼠分为模型组(model组)、二甲双胍组(Met组,20 mg/kg)、NAR低(NAR-L,50 mg/kg)、高(NAR-H,100 mg/kg)剂量组和NAR+EX527组(NAR 100 mg/kg+EX52710 mg/kg),每组10只。Met组和NAR低、高剂量组大鼠灌胃给予相应剂量的药物,NAR+EX527组大鼠在灌胃给予NAR的同时腹腔注射EX527,1次/d,连续给药28 d。检测大鼠空腹血糖(FBG)、空腹胰岛素(FINS)水平,计算胰岛素抵抗指数(HOMA-IR);检测血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)水平;检测胰腺组织丙二醛(MDA)水平和超氧化物歧化酶(SOD)、谷胱甘肽过氧化酶(GSH-Px)活性;HE染色观察胰腺和胎盘组织病变;Western blotting法检测胰腺组织腺苷酸活化蛋白激酶(AMPK)、p-AMPK、沉默信息调节因子1(SIRT1)、过氧化物酶体增殖物激活受体γ共激活因子1α(PGC-1α)蛋白表达。结果与control相比,model组大鼠FBG、FINS、HOMA-IR、血清TC、TG、LDL-C水平、胰腺组织MDA水平显著升高,SOD和GSH-Px活性、胰腺组织中p-AMPK/AMPK比值和SIRT1、PGC-1α表达水平显著降低(P<0.05),胎盘和胰腺组织出现明显病理损伤;与model组比较,Met组和NAR-L、NAR-H组大鼠FBG、FINS、HOMA-IR、血清TC、TG、LDL-C水平、胰腺组织MDA水平显著降低,SOD和GSH-Px活性、胰腺组织中p-AMPK/AMPK比值和SIRT1、PGC-1α表达水平显著升高(P<0.05),胎盘和胰腺组织损伤减少;且在NAR干预的基础上,使用SIRT1抑制剂EX527可明显逆转NAR对GDM大鼠的保护作用。结论NAR可能通过激活SIRT1/PGC-1α通路改善GDM大鼠糖脂代谢紊乱和氧化应激反应。ObjectiveTo explore the effect and mechanism of naringenin(NAR)on glucose and lipid metabolism and oxidative stress in rats with gestational diabetes mellitus(GDM).Methods10 normal pregnant rats were selected as the control group,and the GDM model was prepared.One-time tail iv streptozotocin(STZ,35 mg/kg)was used to construct GDM model.The 50 rats successfully modeled were divided into model group,metformin group(Met group,20 mg/kg),low NAR(NAR-L,50 mg/kg),high(NAR-H,100 mg/kg)dose groups and NAR+EX527 group(NAR 100 mg/kg+EX52710 mg/kg),10 rats per group.Rats in Met group and NAR low-dose and high-dose groups were given corresponding doses of drugs ig.Rats in NAR+EX527 group were given NAR ig and EX527 ip at the same time,once a day,for 28 consecutive days.The levels of fasting blood glucose(FBG)and fasting serum insulin(FINS)in rats were detected,and the homeostasis model assessment for insulin resistance(HOMA-IR)was calculated;the levels of serum triglycerides(TG),cholesterol(TC)and low density lipoprotein cholesterol(LDL-C)were detected;the level of malondialdehyde(MDA)in pancreatic tissue and the activity of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)were detected;the tissue lesions of pancreas and placenta were observed with HE staining;the expression of pancreatic tissue AMP-activated protein kinase(AMPK),p-AMPK,silent information regulator 1(SIRT1),peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α)proteins was detected with Western blotting method.ResultsCompared with control,the FBG,FINS,HOMA-IR,serum TC,TG,LDL-C levels,and pancreatic tissue MDA level in the model group were significantly increased,the SOD and GSH-Px activities,pancreatic tissue p-AMPK/AMPK ratio and SIRT1 and PGC-1αexpression levels were significantly reduced(P<0.05),and the placenta and pancreas tissues showed obvious pathological damage;Compared with the model group,the FBG,FINS,HOMA-IR,serum TC,TG,LDL-C levels,and pancreatic tissue MDA level in the Met group and the NAR-L and NAR-H groups were signif

关 键 词：妊娠期糖尿病 柚皮素 糖脂代谢紊乱 氧化应激 沉默信息调节因子1 过氧化物酶体增殖物激活受体γ共激活因子1α 

分 类 号：R714.256[医药卫生—妇产科学]