基于Nrf2/HO-1通路探究虎杖苷对妊娠期糖尿病大鼠的治疗效果及作用机制  

Exploring the therapeutic effects and action mechanism of polydatin on gestational diabetes mellitus rats based on Nrf2/HO-1 pathway

作　　者：周芳芳 刘宇[1] 马双玲 李晓倩 张新宁 李辞妹[1] 毕晶晶 李国芸[1] ZHOU Fangfang;LIU Yu;MA Shuangling;LI Xiaoqian;ZHANG Xinning;LI Cimei;BI Jingjing;LI Guoyun(Department of Obstetrics 1,Xinxiang Central Hospital,Xinxiang 453099,China)

机构地区：[1]新乡市中心医院产科一,新乡453099

出　　处：《天津中医药大学学报》2024年第7期610-616,共7页Journal of Tianjin University of Traditional Chinese Medicine

基　　金：2019年度河南省医学科技攻关计划(联合共建)项目(LHGJ20191328)。

摘　　要：[目的]探究虎杖苷(PD)对妊娠期糖尿病(GDM)大鼠的治疗效果及作用机制。[方法]高脂高糖喂养雌性SD大鼠8周,雌雄同笼制备孕鼠84只,随机分为7组(12只/组):空白组、模型组、PD低、中、高剂量组(30、75、150 mg/kg的PD)、阳性对照组(200 mg/kg盐酸二甲双胍)、抑制剂组[150 mg/kg的PD+30 mg/kg的核转录因子E2相关因子2(Nrf2)/血红素加氧酶-1(HO-1)通路抑制剂ML385],除空白组外,其余各组在妊娠5 d后,腹腔注射链脲佐菌素(35 mg/kg)复制GDM大鼠模型。测量各组孕鼠体质量及空腹血糖(FBG);酶联免疫吸附(ELISA)法测定大鼠空腹胰岛素(FINS)、白细胞介素(IL)-6、IL-1β、肿瘤坏死因子(TNF)-α水平,计算胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)、胰岛素敏感指数(ISI);全自动生化分析仪分析大鼠血清中血脂水平;苏木精-伊红(HE)染色观察大鼠胰腺组织损伤;蛋白免疫印迹(Western Blot)法检测各组大鼠胰腺组织中Nrf2/HO-1信号通路蛋白表达。[结果]与空白组比较,模型组大鼠体质量、FBG、FINS、HOMA-IR、IL-6、IL-1β、TNF-α水平、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、游离脂肪酸(FFA)含量升高,ISI、HOMA-β、高密度脂蛋白胆固醇(HDL-C)含量、胰岛数量、Nrf2、HO-1蛋白表达水平降低(P<0.05);与模型组比较,PD低、中、高剂量组大鼠体质量、FBG、FINS、HOMA-IR、IL-6、IL-1β、TNF-α水平、TC、TG、LDL-C、FFA含量降低,ISI、HOMA-β、HDL-C含量、胰岛数量、Nrf2、HO-1蛋白表达水平升高(P<0.05);与阳性对照组比较,PD高剂量组大鼠上述指标差异均无统计学意义(P>0.05),提示与阳性对照药物疗效相当;Nrf2/HO-1通路抑制剂ML385可以逆转高剂量PD对GDM大鼠的保护作用(P<0.05)。[结论]PD通过降低血糖、血脂和炎症反应来改善GDM,其作用机制可能与激活Nrf2/HO-1信号通路有关。[Objective]To explore the therapeutic effect and action mechanism of polydatin(PD)on gestational diabetes mellitus(GDM)rats.[Methods]Female SD rats were fed with high fat and high sugar for 8 weeks,and 84 pregnant rats were prepared in the same cage.They were randomly grouped into 7 groups(12 rats/group):control group,Model group,PD low,medium,and high dosage groups(30,75,150 mg/kg),positive control group(200 mg/kg metformin hydrochloride),and inhibitor group[150 mg/kg PD+30 mg/kg nuclear factor erythroid-2 related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway inhibitor ML385].Except for the control group,the other groups were intraperitoneally injected with streptozotocin(35 mg/kg)to replicate the GDM rat model after 5 days of pregnancy.The body mass and fasting blood glucose(FBG)of pregnant rats in each group were measured;the levels of fasting insulin(FINS),interleukin(IL)-6,IL-1βand tumor necrosis factor(TNF)-αwere measured by ELISA,the homeostasis model assessment-IR(HOMA-IR),isletβcell function index(HOMA-β)and insulin sensitive index(ISI)were calculated;the levels of serum lipids in rats were analyzed by automatic biochemical analyzer;HE staining was used to observe the damage of pancreatic tissue in rats;Western Blot was applied to detect the expression of Nrf2 and HO-1 signal pathway proteins in the pancreas of rats in each group.[Results]Compared with the control group,the body mass,the levels of FBG,FINS,HOMA-IR,IL-6,IL-1β,TNF-α,the contents of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),free fat acid(FFA)in the model group were obviously increased,the contents of ISI,HOMA-β,high-density lipoprotein cholesterol(HDL-C),the number of islets,the expression of Nrf2 and HO-1 proteins were obviously decreased(P<0.05);compared with the model group,the body mass,the levels of FBG,FINS,HOMA-IR,IL-6,IL-1β,TNF-α,the contents of TC,TG,LDL-C,FFA in the low,middle and high dose PD groups were obviously decreased,the contents of ISI,HOMA-β,HDL-C,the number of islets,the

关 键 词：虎杖苷 核转录因子E2相关因子2/血红素加氧酶-1 妊娠期糖尿病 作用机制 

分 类 号：R285.5[医药卫生—中药学]