熟地黄对雌性中枢性性早熟大鼠下丘脑-垂体-IGF-1轴影响的实验研究  

Experimental study on effect of rehmanniae radix praeparata on hypothalamic-pituitary-IGF-1 axis in female central precocious puberty rats

作　　者：詹红艳[1] 龙海旭 陆影[1] 狄雯雯[1] 李巧香[1] ZHAN Hongyan;LONG Haixu;LU Ying;DI Wenwen;LI Qiaoxiang(Department of Pediatrics,The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine,Changsha 410005,China)

机构地区：[1]湖南中医药大学附属第二医院儿科,湖南长沙410005

出　　处：《西部医学》2024年第12期1729-1733,共5页Medical Journal of West China

基　　金：湖南省中医药管理局中医药科研计划项目(B2023148)。

摘　　要：目的 探讨熟地黄对雌性中枢性性早熟(CPP)大鼠的治疗作用,并阐明其可能的作用机制。方法 将48只SPF级雌性28日龄SD大鼠随机分为正常组、模型组、阳性对照(亮丙瑞林100μg/kg)组和熟地黄低、中、高剂量(0.8、1.6、3.2 g/kg)组,每组8只。采用N-甲基-DL-天冬氨酸(NMA)法建立CPP大鼠模型,造模期间同时给予亮丙瑞林或不同剂量熟地黄干预,每天1次;记录大鼠阴道开口时间及首个动情间期时间;HE染色检测大鼠子宫内膜厚度及卵巢黄体个数;ELISA检测大鼠血清中促黄体生成激素(LH)、卵泡刺激素(FSH)、雌二醇(E2)水平;Western blot检测大鼠下丘脑中性腺激素释放激素(GnRH)、胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)及生长激素(GH)蛋白表达水平。结果 与正常组比较,模型组大鼠阴道开口及首个动情间期时间明显提前(均P<0.05);子宫壁厚度和卵巢黄体数显著增加,同时血清中LH、FSH、E2水平以及下丘脑组织中GnRH、IGF-1、IGFBP-3、GH蛋白表达水平显著升高(均P<0.05)。与模型组比较,阳性对照组及熟地黄各剂量组大鼠阴道开口时间及首个动情间期时间明显较长(均P<0.05);子宫壁厚度和卵巢黄体数显著减少,同时血清中LH、FSH、E2水平以及下丘脑组织中GnRH、IGF-1、IGFBP-3、GH蛋白表达水平显著降低(均P<0.05)。结论 熟地黄可降低CPP大鼠机体生长激素水平,抑制性早熟表现,其机制可能与延缓下丘脑-垂体-IGF-1轴启动有关。Objective To investigate the therapeutic effect of rehmanniae radix praeparata on female central precocious puberty(CPP)rats and elucidate its possible mechanism.Methods Forty-eight 28-day-old female SD rats were randomly divided into normal group,model group,positive control(leuprorelin 100μg/kg)group,and low-,medium-,and high-dose rehmanniae radix praeparata(0.8,1.6,3.2 g/kg)groups,with 8 rats in each group.The CPP rat model was established by N-methyl-DL-aspartate(NMA)method,during the modeling period,the rats were treated with leuprorelin or different doses of rehmanniae radix praeparata,once a day until available.The time of vaginal opening and the first interestrus were recorded.HE staining was used to detect the endometrial thickness and the number of ovarian corpus luteum.The levels of luteinizing hormone(LH),follicle stimulating hormone(FSH)and estradiol(E2)in serum were detected by ELISA.The protein expression levels of gonadotropin-releasing hormone(GnRH),insulin-like growth factor-1(IGF-1),insulin-like growth factor binding protein-3(IGFBP-3)and growth hormone(GH)in the hypothalamus of rats were detected by Western blot.Results Compared with normal group,the time of vaginal opening and first estrus interval in the model group was significantly shorter(all P<0.05).The thickness of the uterine wall and the number of the corpus luteum of the ovary were significantly increased,while the levels of LH,FSH and E2 in serum and the protein expression levels of GnRH,IGF-1,IGFBP-3 and GH in hypothalamus were significantly increased(all P<0.05).Compared with model group,the time of vaginal opening and first estrus interval in the positive control group and rehmanniae radix praeparata dose groups were significantly longer(all P<0.05).The thickness of the uterine wall and the number of the corpus luteum of the ovary were significantly decreased,while the levels of LH,FSH and E2 in serum and the protein expression levels of GnRH,IGF-1,IGFBP-3 and GH in hypothalamus were significantly decreased(all P<0.05).Conclusio

关 键 词：熟地黄 中枢性性早熟 下丘脑 垂体 胰岛素样生长因子-1 

分 类 号：R-332[医药卫生]