摘要
目的研究黄芪甲苷对肥胖型多囊卵巢综合征(PCOS)大鼠胰岛素抵抗(IR)的改善作用,并分析对其卵巢MAPK/ERK通路的影响。方法来曲唑联合高脂高糖饮食法构建肥胖PCOS大鼠模型,随机分为模型组、二甲双胍(135 mg/kg)组和低、高剂量黄芪甲苷(25、50 mg/kg)组,每组8只,另设对照组,连续灌胃给药21 d后,记录体质量,计算卵巢指数,测定空腹血糖(FBG)、血清甘油三酯(TG)、总胆固醇(TC)、促卵泡激素(FSH)、睾酮(T)、雌二醇(E_(2))、促黄体生成素(LH)及空腹胰岛素(FINS)水平,计算HOMA-IR和LH/FSH值,HE染色观察卵巢组织形态,Western blot法检测卵巢组织MAPK/ERK通路相关蛋白表达,免疫荧光法检测卵巢组织血管内皮生长因子(VEGF)蛋白表达。结果与对照组比较,模型组大鼠卵巢形态呈多囊样病态改变,体质量、卵巢指数、血清TG、TC、LH、FSH、T、FINS、FBG水平、LH/FSH和HOMA-IR值、卵巢组织p-ERK1/2/ERK1/2、p-MEK1/2/MEK1/2、p-Raf/Raf、VEGF蛋白表达升高(P<0.01),血清E_(2)水平降低(P<0.01);与模型组比较,黄芪甲苷各剂量组和二甲双胍组大鼠卵巢多囊样病变明显缓解,体质量、卵巢指数、血清TG、TC、LH、FSH、T、FINS、FBG水平、LH/FSH和HOMA-IR值、卵巢组织p-ERK1/2/ERK1/2、p-MEK1/2/MEK1/2、p-Raf/Raf、VEGF蛋白表达降低(P<0.05,P<0.01),血清E_(2)水平升高(P<0.05,P<0.01)。结论黄芪甲苷可拮抗肥胖PCOS大鼠IR,改善激素水平,减轻其卵巢病变,该作用可能与抑制MAPK/ERK通路活化有关。
AIM To investigate the effects of astragaloside IV on improving insulin resistance(IR)in obese rat model of polycystic ovary syndrome(PCOS),and to analyze its effect on ovarian MAPK/ERK pathway as well.METHODS The obese PCOS rat models established by feeding of letrozole combined with high-fat and high-sugar diet were randomly divided into the model group,the metformin(135 mg/kg)group and the low-dose and high-dose astragalosideⅣ(25,50 mg/kg)groups,with 8 rats in each group in contrast to those of the control group.After 21 days oral administration,the rats had their body weight recorded;their ovarian index calculated;their levels of fasting blood glucose(FBG),serum triglyceride(TG),total cholesterol(TC),follicle-stimulating hormone(FSH),testosterone(T),estradiol(E_(2)),luteinizing hormone(LH)and fasting insulin(FINS)measured;their HOMA-IR and LH/FSH values calculated;their ovarian expressions of MAPK/ERK pathway related proteins detected by Western blot;and their ovarian expression of vascular endothelial growth factor(VEGF)protein detected by immunofluorescence staining.RESULTS Compared with the control group,the model group showed increased polycystic pathological changes,levels of body weight,ovarian index,serum TG,TC,LH,FSH,T,FINS,and FBG,values of LH/FSH and HOMA-IR,and ovarian p-ERK1/2/ERK1/2,p-MEK1/2/MEK1/2,p-Raf/Raf,and VEGF protein expressions(P<0.01);and decreased serum E_(2) level(P<0.01).Compared with the model group,both astragalosideⅣand metformin groups shared significantly alleviated ovarian polycystic lesions,and decreased body weight,levels of ovarian index,serum TG,TC,LH,FSH,T,FINS,and FBG,values of LH/FSH and HOMA-IR,ovarian p-ERK1/2/ERK1/2,p-MEK1/2/MEK1/2,p-Raf/Raf,and VEGF protein expressions(P<0.05,P<0.01),and increased serum E_(2) level(P<0.05,P<0.01).CONCLUSION Upon the obese PCOS rat models,astragalosideⅣcan antagonize their IR,improve their hormone levels and alleviate their ovarian lesions via inhibiting the activation of MAPK/ERK pathway.
作者
刘冷
贺春花
LIU Leng;HE Chun-hua(Department of Gynaecology,Jingmen Central Hospital,Jingmen 448001,China)
出处
《中成药》
CAS
CSCD
北大核心
2024年第1期94-100,共7页
Chinese Traditional Patent Medicine
基金
荆门市科技计划项目(2019YFYB024)。