九味楮实颗粒调控下丘脑PI3K/Akt/mTOR/KISS-1信号通路对中枢性性早熟大鼠的干预作用  

Effect of Jiuwei Chushi granule on central precocious puberty in ratsVia hypothalamic PI3K/Akt/mTOR/KISS-1 axis

作　　者：唐卓婷 于晓林 王奕辰 鲁艳芳[1] TANG Zhuoting;YU Xiaolin;WANG Yichen;LU Yanfang(Hubei Provincial Hospital of Traditional Chinese Medicine,Wuhan 430000,Hubei,China)

机构地区：[1]湖北省中医院,湖北武汉430000

出　　处：《现代中西医结合杂志》2025年第6期739-744,836,共7页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：湖北省卫生健康委科研项目(WJ2021M249)。

摘　　要：目的观察九味楮实颗粒对中枢性性早熟(CPP)大鼠的干预作用,并基于下丘脑磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)/KISS-1信号通路探讨其作用机制。方法将60只雌性SD大鼠按体重随机分为正常组、模型组、戈那瑞林组及九味楮实颗粒高剂量组、中剂量组、低剂量组,每组10只。除正常组外,其余5组大鼠均采用N-甲基-DL-天冬氨酸(NMA)皮下注射方法建立CPP模型。在造模期间,戈那瑞林组给予戈那瑞林100μg/kg皮下注射,九味楮实颗粒高、中、低剂量组分别给予九味楮实颗粒69.48 g/kg、34.74 g/kg、17.37 g/kg灌胃,正常组、模型组给予等体积生理盐水灌胃,均1次/d,于大鼠第1个发情前期停止。观察大鼠首次阴道口开放时间,计算子宫、卵巢系数,ELISA法检测血清雌二醇(E_(2))、促黄体生成素(LH)、促卵泡激素(FSH)水平,q-PCR法检测下丘脑组织中胰岛素样生长因子-1(IGF-1)、促性腺激素释放激素(GnRH)、G蛋白偶联受体54(GPR54)mRNA表达情况,Western blot法检测下丘脑组织中PI3K/Akt/mTOR/KISS-1信号通路蛋白表达情况。结果与正常组比较,模型组大鼠阴道口开放时间明显提前(P<0.05),子宫系数、血清性激素(E_(2)、LH、FSH)水平和下丘脑组织中IGF-1、GnRH、GPR54 mRNA相对表达量及PI3K、Akt、p-mTOR、KISS-1蛋白相对表达量均明显升高(P均<0.05)。与模型组比较,各药物组大鼠阴道口开放时间均明显推迟(P均<0.05),血清性激素(E_(2)、LH、FSH)水平和下丘脑组织中GnRH、GPR54 mRNA相对表达量及KISS-1蛋白相对表达量均明显降低(P均<0.05);戈那瑞林组和九味楮实颗粒中剂量组大鼠子宫系数均明显降低(P均<0.05),戈那瑞林组和九味楮实颗粒高、中剂量组大鼠下丘脑组织中IGF-1 mRNA相对表达量及PI3K、Akt、p-mTOR蛋白相对表达量均明显降低(P均<0.05)。结论九味楮实颗粒可调节CPP大鼠性激素水平,抑制性早熟,其作�Objective It is to observe the intervention effect of Jiuwei Chushi granule on central precocious puberty(CPP)in rats,and to exlpore its mechanism based on the hypothalamic phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/KISS-1 signaling pathway.Methods Sixty female SD rats were randomly divided into normal group,model group,Gonadorelin group,high dose,medium dose and low dose groups of Jiuwei Chushi granule according to their body weight.The rats of all groups except for the normal group were given N-methyl-DL-aspartic acid(NMA)by subcutaneous injection to establish models of CPP.During modeling,the Gonadorelin group was given Gonadorelin 100μg/kg by subcutaneous injection,while the high dose,medium dose,and low dose groups of Jiuwei Chushi granule were respectively given Jiuwei Chushi granule 69.48 g/kg,34.74 g/kg,and 17.37 g/kg by gavage,the normal group and model group were given equivalent volumes of normal saline,the treatments were administered once daily until the first proestrus phase.The first vaginal opening time of the rats was observed,the uterine and ovarian coefficients were calculated,the serum levels of estradiol(E_(2)),luteinizing hormone(LH)and follicle stimulating hormone(FSH)were detected by ELISA,the mRNA expressions of insulin-like growth factor-1(IGF-1),gonadotropin-releasing hormone(GnRH)and G protein coupled receptor 54(GPR54)in hypothalamic tissue were detected by q-PCR,and the protein expressions of PI3K/Akt/mTOR/KISS-1 signaling pathway in hypothalamic tissue were detected by Western-blot.Results The vaginal opening time of rats in the model group was significantly earlier than that of rats in the normal group(P<0.05),and the uterine coefficients,serum levels of sex hormone(E_(2),LH,FSH),the relative mRNA expressions of IGF-1,GnRH and GPR54 mRNA in hypothalamic tissues as well as the relative protein expressions of PI3K,Akt,p-mTOR and KISS-1 protein in hypothalamic tissues were all significantly higher than those of rats in the normal gro

关 键 词：中枢性性早熟 雌性大鼠 九味楮实颗粒 下丘脑磷脂酰肌醇3-激酶 蛋白激酶B 哺乳动物雷帕霉素靶蛋白 KISS-1 

分 类 号：R-332[医药卫生]