木犀草素对妊娠糖尿病大鼠胎盘功能障碍的改善作用及机制  

Improving effect and its mechanism of luteolin on placental dysfunction in rats with gestational diabetes mellitus

作　　者：胡殿鹏[1] 张举[2] 侯奕忻 程琳[1] 卢佳璐 HU Dianpeng;ZHANG Ju;HOU Yixin;CHENG Lin;LU Jialu(Dept.of Basic Medicine,Nanyang Medical College,Nanyang Henan 473000,China;Dept.of Obstetrics,the First Affiliated Hospital of Nanyang Medical College,Nanyang Henan 473000,China)

机构地区：[1]南阳医学高等专科学校基础医学部,河南南阳473000 [2]南阳医学高等专科学校第一附属医院产科,河南南阳473000

出　　处：《中国药房》2024年第22期2763-2768,共6页China Pharmacy

基　　金：南阳市科技计划项目(No.KJGG196);河南省社会科学界联合会调研课题(No.SKL-2019-589)。

摘　　要：目的基于hedgehog(Hh)信号通路探讨木犀草素(Lut)对妊娠糖尿病(GDM)大鼠胎盘功能障碍的改善作用及潜在机制。方法随机选择雌鼠20只作为对照组,以正常饲料喂养。剩余雌鼠以高脂高糖饲料喂养8周后与雄性大鼠合笼,取妊娠大鼠,腹腔注射35 mg/kg的链脲佐菌素以构建GDM雌鼠模型;将造模成功的雌鼠随机分为模型组、SAG组(Hh信号通路激活剂SAG 50 mg/kg)、Lut低剂量组(Lut 40 mg/kg)、Lut高剂量组(Lut 80 mg/kg)、Lut高+ITR组(Lut 80 mg/kg+Hh信号通路拮抗剂伊曲唑康50 mg/kg),每组20只。各药物组雌鼠灌胃相应药液,每天1次,持续19 d。末次给药后,检测各组雌鼠的糖脂代谢参数(空腹血糖、空腹胰岛素水平和胰岛素抵抗指数)、胎盘质量和通透性[以伊文思蓝(EB)含量表示],观察其胎盘组织病理变化,检测其胎盘组织中超氧化物歧化酶(SOD)活性及丙二醛(MDA)、还原型谷胱甘肽(GSH)含量以及Sonic Hh(Shh)、Patched-1(Ptch1)、Smoothened(Smo)、Gil家族锌指蛋白1(Gli1)的表达水平。结果与对照组相比,模型组大鼠胎盘组织中毛细血管管腔狭窄,血管周围可见纤维化区域;其糖脂代谢参数、胎盘质量、EB及MDA含量均显著升高,SOD活性、GSH含量及Shh、Ptch1、Smo、Gli1蛋白的表达水平均显著降低(P<0.05)。与模型组相比,SAG组和Lut低、高剂量组大鼠胎盘组织中毛细血管管腔变宽,血管周围纤维化明显减少;糖脂代谢参数、胎盘质量、EB及MDA含量均显著降低,SOD活性、GSH含量及Shh、Ptch1、Smo、Gli1蛋白的表达水平均显著升高(P<0.05);且Lut高剂量组上述参数与SAG组相比差异均无统计学意义(P>0.05)。Hh信号通路拮抗剂伊曲唑康可显著逆转Lut对上述指标的改善作用(P<0.05)。结论Lut可改善GDM大鼠的糖代谢参数,降低胎盘通透性,减轻其胎盘组织病理损伤和氧化应激,上述作用可能与激活Hh信号通路有关。OBJECTIVE To explore the improving effect of luteolin(Lut)on placental dysfunction in rats with gestational diabetes mellitus(GDM)and its potential mechanism based on hedgehog(Hh)signaling pathway.METHODS Twenty female rats were randomly selected as a control group and fed a normal diet.The remaining female rats were fed a high-fat and high-sugar diet for 8 weeks and then caged with male rats.Pregnant rats were administered 35 mg/kg streptozotocin intraperitoneally to establish GDM models.Successfully modeled female rats were randomly allocated to model group,SAG group(Hh signaling pathway activator SAG 50 mg/kg),Lut low-dose group(Lut 40 mg/kg),Lut high-dose group(Lut 80 mg/kg),and Lut high+ITR group(Lut 80 mg/kg+Hh signaling pathway antagonist itraconazole 50 mg/kg),with 20 rats in each group.Female rats in each drug group were intubated with the corresponding drug solution once a day for 19 days.After the final administration,the serum glucosefat metabolic parameters(levels of fasting blood glucose and fasting insulin,insulin resistance index),placental quality,placental permeability[Evan’s blue(EB)content],and pathological changes in placental tissue were observed.The activities of superoxide dismutase(SOD),the contents of malondialdehyde(MDA)and reduced glutathione(GSH),and the protein expressions of Sonic Hh(Shh),Patched-1(Ptch1),Smoothened(Smo)and Gli family zinc finger-1(Gli1)in placental tissue were detected.RESULTS Compared with the control group,rats in the model group showed narrow capillary lumens,perivascular fibrosis in placental tissue,and a significant increase in serum glucose-fat metabolic parameters,placental quality,contents of EB and MDA,while there was a significant decrease in SOD activity,GSH content,and protein expressions of Shh,Ptch1,Smo and Gli1(P<0.05).Compared with the model group,rats in the SAG group,Lut low-dose and high-dose groups had widened capillary lumens,a significant decrease in perivascular fibrosis in placental tissue,serum glucose-fat metabolic parameters,placental q

关 键 词：木犀草素 妊娠糖尿病 胎盘功能障碍 HEDGEHOG信号通路 

分 类 号：R965[医药卫生—药理学] R714.256[医药卫生—药学]