地黄多糖对妊娠合并甲状腺功能亢进小鼠子代肾损伤的影响及机制  

Effect and mechanism of rehmannia polysaccharide on the renal injury in offspring of pregnant mice with hyperthyroidism

作　　者：李玉琴[1] 俄洛吉[1] 巩海凤 汪玉凤[1] 曾湘晖[1] Li Yu-Qin;Oroji;Gong Hai-Feng;Wang Yu-Feng;Zeng Xiang-Hui(Department of Obstetrics,People's Hospital of Qinghai Province,Xining 810000,China)

机构地区：[1]青海省人民医院产科,西宁810000

出　　处：《解放军医学杂志》2021年第11期1061-1067,共7页Medical Journal of Chinese People's Liberation Army

基　　金：青海省科学技术项目(26347076)。

摘　　要：目的探讨地黄多糖对妊娠合并甲状腺功能亢进(简称甲亢)小鼠子代肾损伤的影响,以及对核因子E2相关因子(Nrf2)/血红素氧合酶(HO-1)/Nod样受体蛋白3(NLRP3)信号通路的调节作用。方法56只成功受孕的昆明雌鼠随机分为正常组(n=12)、模型组(n=12)、阳性对照组(n=10)、地黄多糖低剂量组(n=11)和地黄多糖高剂量组(n=11),建立妊娠合并甲亢模型。阳性对照组给予甲巯咪唑5 mg/kg灌胃,低、高剂量组分别给予地黄多糖20和40 mg/kg灌胃,1次/d,直至分娩。称取母鼠体重,ELISA检测母鼠血清中游离三碘甲腺原氨酸(FT_(3))、游离甲状腺素(FT_(4))、促甲状腺激素(TSH)含量,HE染色观察仔鼠肾组织,全自动生化分析仪检测仔鼠血清中尿素氮(BUN)和肌酐(Cr)含量,ELISA检测仔鼠肾组织中超氧化物歧化酶(SOD)活性及丙二醛(MDA)、白细胞介素(IL)-1β、IL-18含量,Western blotting检测仔鼠肾组织中Nrf2、HO-1和NLRP3蛋白相对表达量。结果HE染色结果显示,模型组仔鼠肾小管和肾小球结构紊乱,基底膜明显增厚,大量红细胞浸润,内皮细胞水肿明显;阳性对照组、地黄多糖低剂量和高剂量组仔鼠肾组织病变较模型组明显减轻。模型组小鼠体重明显低于正常组,而阳性对照组、地黄多糖低剂量和高剂量组小鼠体重明显高于模型组,差异均有统计学意义(P<0.05)。ELISA检测结果显示,模型组小鼠血清FT_(3)和FT_(4)含量明显高于正常组,TSH含量明显低于正常组;而阳性对照组、地黄多糖低剂量和高剂量组血清FT_(3)和FT_(4)含量低于模型组,TSH含量高于模型组,差异均有统计学意义(P<0.05)。模型组仔鼠血清BUN和Cr含量均高于正常组,阳性对照组、地黄多糖低剂量和高剂量组血清BUN及Cr含量均低于模型组,差异均有统计学意义(P<0.05)。ELISA检测结果显示,模型组仔鼠肾组织中MDA、IL-1β及IL-18含量均高于正常组,SOD活性低于正常组;而阳性对照组、地�Objective To investigate the effect of rehmannia polysaccharide on the renal injury in offspring of pregnant mice with hyperthyroidism,and on regulating the signaling pathway of nuclear factor E2-related factor(Nrf2)/heme oxygenase(HO-1)/Nod-like receptor protein 3(NLRP3).Methods Fifty-six female kunming mice pregnant successfully were randomly divided into normal group(n=12),model group(n=12),positive control group(n=10),rehmannia polysaccharide low-dose group(n=11)and rehmannia polysaccharide high-dose group(n=11)to establish pregnancy with hyperthyroidism model.The positive control group was given methimazole 5 mg/kg intragastric administration,and the low and high dose groups were given rehmannia polysaccharide 20 and 40 mg/kg intragastric administration respectively,once a day,until delivery.The body weight of female mice was measured,and the contents of free triiodothyronine(FT_(3)),free thyroxine(FT_(4))and thyroid stimulating hormone(TSH)in the serum were detected by ELISA.Kidney tissue of young mice was observed by HE staining.The contents of urea nitrogen(BUN)and creatinine(Cr)in the serum of the young mice were detected by automatic biochemical analyzer.Superoxide dismutase(SOD)activity,malondialdehyde(MDA)content,interleukin(IL)-1βand IL-18 content were detected by ELISA,and the relative expression levels of Nrf2,HO-1 and NLRP3 proteins were detected by Western blotting.Results HE staining showed that the renal tubules and glomerulus in model group were disorganized,the basement membrane thickened significantly,large number of red blood cells infiltrated,and endothelial cells were edema.Compared with model group,the kidney tissue lesion reduced obviously in positive control group and rehmannia polysaccharide low and high dose group.The body weight of mice was significantly lower in model group than that in normal group,while was significantly higher in positive control group and rehmannia polysaccharide low-dose and high-dose groups than that in model group with statistical significance(P<0.05).ELISA

关 键 词：妊娠 甲状腺功能亢进 肾损伤 地黄多糖 Nrf2/HO-1/NLRP3通路 

分 类 号：R285.5[医药卫生—中药学]