葛根汤对原发性痛经小鼠下丘脑-垂体-卵巢轴的调节作用研究  

Regulating effect of Gegen Decoction on hypothalamic-pituitary-ovarian axis in mice with primary dysmenorrhea

作　　者：肖娜 钱依文 柴程芝 XIAO Na;QIAN Yi-wen;CHAI Cheng-zhi(Department of Pharmacology of Chinese Materia Medica,School of Traditional Chinese Pharmacy,China Pharmaceutical University,Nanjing 211198,China;Jiangsu Key Laboratory of Traditional Chinese Medicine Evaluation and Translational Research,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学中药学院中药药理与中医药学系,江苏南京211198 [2]中国药科大学江苏省中药评价与转化重点实验室,江苏南京211198

出　　处：《中国中药杂志》2024年第12期3288-3294,共7页China Journal of Chinese Materia Medica

摘　　要：探讨葛根汤对原发性痛经(primary dysmenorrhea, PD)小鼠下丘脑-垂体-卵巢轴(hypothalamic-pituitary-ovarian axis, HPOA)功能失调的调节作用。采用苯甲酸雌二醇-缩宫素联用构建周期性PD小鼠模型,将40只小鼠随机分为空白组、模型组、葛根汤组和布洛芬组,检测各组小鼠扭体反应,下丘脑、垂体、卵巢、子宫脏器指数,ELISA法检测血清中前列腺素F_(2α)(prostaglandin F_(2α), PGF_(2α))、促性腺激素释放激素(gonadotropin-releasing hormone, GnRH)、促卵泡生成素(follicle-stimulating hormone, FSH)、促黄体生成素(luteinizing hormone, LH)、雌激素(estrogen, E_(2))含量,Western blot法检测垂体组织中促性腺激素释放激素受体(gonadotropin-releasing hormone receptor, GnRH-R)、卵巢组织中促卵泡生成素受体(follicle-stimulating hormone receptor, FSHR)和促黄体生成素受体(luteinizing hormone receptor, LHR)、子宫组织中雌激素受体(estrogen receptors, ER)蛋白表达水平,RT-qPCR法检测小鼠垂体组织中GnRH-R、卵巢组织中FSHR和LHR、子宫组织中ER mRNA表达水平,免疫荧光检测子宫组织ER蛋白表达。结果显示,模型组小鼠扭体评分,血清中PGF_(2α)、GnRH、FSH、LH、E_(2)含量以及卵巢及子宫系数,垂体组织中GnRH-R、卵巢组织中FSHR和LHR、子宫组织中ER的蛋白及基因表达显著升高;与模型组相比,葛根汤能抑制扭体反应,降低血清中PGF_(2α)、GnRH、FSH、LH、E_(2)含量和卵巢及子宫系数,下调垂体组织中GnRH-R、卵巢组织中FSHR和LHR、子宫组织中ER的蛋白及基因表达。提示葛根汤对PD小鼠的HPOA具有调节作用,通过下调HPOA相关蛋白及基因表达进而抑制E_(2)生成,可能是其发挥治疗PD的作用机制。This study aimed to explore the regulating effect of Gegen Decoction(GGD)on the hypothalamic-pituitary-ovarian axis(HPOA)dysfunction in the mouse model of primary dysmenorrhea(PD).The mouse model of PD with periodic characteristics was established by administration of estradiol benzoate and oxytocin.Mice were randomized into control,model,GGD,and ibuprofen groups.The writhing response,hypothalamus index,pituitary index,ovary index,and uterus index were observed and determined.The serum levels of prostaglandin F_(2α)(PGF_(2α)),gonadotropin-releasing hormone(GnRH),follicle-stimulating hormone(FSH),luteinizing hormone(LH),and estrogen(E_(2))levels were measured by ELISA kits.Western blot and qPCR were employed to determine the protein and mRNA levels,respectively,of gonadotropin-releasing hormone receptor(GnRH-R)in the pituitary tissue,follicle-stimulating hormone receptor(FSHR)and luteinizing hormone receptor(LHR)in the ovarian tissue,and estrogen receptor(ER)in the uterine tissue.The results showed that the writhing response,serum levels of PGF_(2α),GnRH,FSH,LH,and E_(2),ovarian and uterine indexes,the protein and mRNA levels of GnRH-R in the pituitary tissue,FSHR and LHR in the ovarian tissue,and ER in the uterine tissue were significantly increased in the model group compared with those in the control group.GGD inhibited the writhing response,reduced the serum levels of PGF_(2α),GnRH,FSH,LH,and E_(2),decreased the ovarian and uterine indexes,and downregulated the protein and mRNA levels of GnRH-R in the pituitary tissue,FSHR and LHR in the ovarian tissue,and ER in the uterine tissue.The data suggested that GGD can regulate the HPOA and inhibit E_(2) generation in the mice experiencing recurrent PD by downregulating the expression of proteins and genes related to HPOA axis,thus exerting the therapeutic effect on PD.

关 键 词：葛根汤 原发性痛经 下丘脑-垂体-卵巢轴 

分 类 号：R285.5[医药卫生—中药学]