摘要
目的探究罗汉果(MG)皂苷提取物是否通过Kelch样ECH相关蛋白1(Keap1)-核因子E2-相关因子2(Nrf2)/抗氧化反应元件(ARE)通路影响妊娠期糖尿病(GDM)大鼠的氧化应激损伤。方法用高脂饮食结合链脲佐菌素多次诱导的方法建立GDM模型大鼠,并分为模型组和低、中、高3个剂量实验组,每组6只;另取同期仅注射同体积枸橼酸-磷酸氢二钠缓冲液的6只妊娠大鼠为对照组。对照组和模型组均予以等量0.9%Na Cl;低、中、高3个剂量实验组分别按50,100和200 mg·kg^-1的剂量灌胃予以60 mg·m L^-1MG皂苷提取物。5组大鼠均每天给药1次,连续给药2周。用免疫组化法检测Keap1、Nrf2和ARE蛋白阳性的表达情况。结果低、中、高3个剂量实验组和模型组、对照组的Keap1阳性表达率分别为(41.16±7.87)%,(28.24±7.16)%,(16.47±6.35)%,(60.64±7.18)%和(11.58±5.13)%,Nrf2阳性表达率分别为(28.63±6.17)%,(43.52±5.37)%,(56.53±7.48)%,(15.16±5.09)%和(68.62±6.23)%,ARE阳性表达率分别为(22.14±5.27)%,(37.72±5.15)%,(49.17±6.74)%,(9.27±4.57)%和(54.17±6.74)%,低、中、高3个剂量实验组和对照组的上述指标与模型组比较,差异均有统计学意义(均P<0.05)。结论MG皂苷提取物可通过激活Keap1-Nrf2/ARE通路缓解GDM大鼠的氧化应激损伤,从而发挥对胰腺组织的保护作用。
Objective To investigate whether Momordica grosvenori(MG)saponin extract plays a protective role in oxidative stress injury of gestational diabetes mellitus(GDM)rats through the Kelch-like ECH associated protein 1-nucleated erythrocyte related factor 2/antioxidant response element(Keap1-Nrf2/ARE)pathway.Methods GDM model rats were established by high-fat diet feeding combined with streptozotocin multiple induction,and were divided into model group and experimental-L,-M,-H groups,with 6 rats per group,another 6 pregnant rats injected with the same volume of citric acid-disodium hydrogen phosphate buffer at the same time were selected as the control group.Control and model groups were given the same amount of 0.9%NaCl.Experimental-L,-M,-H groups were given 60 mg·mL^-1 MG saponin extract by gavage at doses of 50,100 and 200 mg·kg^-1,respectively.Five groups were administered once a day for 2 weeks.The positive expression levels of Keap1,Nrf2 and ARE were detected by immunohistochemistry.Results The positive expression of Keap1 in low,medium and high dose experimental groups,model group and control group were(41.16±7.87)%,(28.24±7.16)%,(16.47±6.35)%,(60.64±7.18)%and(11.58±5.13)%,the positive expression of Nrf2 were(28.63±6.17)%,(43.52±5.37)%,(56.53±7.48)%,(15.16±5.09)%and(68.62±6.23)%,the positive expression of ARE were(22.14±5.27),(37.72±5.15)%,(49.17±6.74)%,(9.27±4.57)%and(54.17±6.74)%.The differences were statistically significant between control,experimental-L,-M,-H groups and model group(all P<0.05).Conclusion MG saponin extract can alleviate oxidative stress injury in GDM rats by activating the Keap1-Nrf2/ARE pathway,and play a protective role in pancreatic tissue.
作者
于万芹
杜晓娜
刘巧敏
杜彦芳
YU Wan-qin;DU Xiao-na;LIU Qiao-min;DU Yan-fang(Department of Obstetrics,The Second Hospital of Hebei Medical University,Shijiazhuang 050000,Hebei Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2019年第21期2723-2727,共5页
The Chinese Journal of Clinical Pharmacology
基金
河北省医学科学研究重点课题基金资助项目(20150250)
关键词
罗汉果皂苷提取物
妊娠期糖尿病
氧化应激损伤
Kelch样ECH相关蛋白1
核红细胞相关因子2
Momordica grosvenori saponin extract
gestational diabetes mellitus
oxidative stress injury
Kelch-like ECH associated protein 1
nucleated erythrocyte related factor 2
