目的 观察加减知柏地黄丸对抑那通诱导的小鼠特发性中枢性性早熟(ICPP)的影响。方法 选用日龄18 d的BALB/c雌性小鼠，随机分为5组:正常对照组，ICPP模型组，加减知柏地黄丸高、低剂量组，甲地孕酮组。除正常对照组外，其他各组均给予外源性促性腺激素释放激素拟似物抑那通复制ICPP模型，并给予不同的药物干预后检测各组小鼠阴道开口数、体质量、血清雌二醇(E2)及黄体生成素(LH)水平，测定子宫、卵巢质量，计算子宫指数和卵巢指数，做子宫和阴道脱落细胞涂片，观察卵巢组织病理学变化等。结果 加减知柏地黄丸高剂量组于造模第2～6天对阴道开口提前有抑制作用(P < 0.05，P < 0.01)，而低剂量组于造模第2～4天对抑那通所致阴道开口提前有抑制作用(P < 0.05，P < 0.01)，甲地孕酮组仅于造模第3天对阴道开口提前有抑制作用(P < 0.05)；加减知柏地黄丸高剂量组和甲地孕酮组均可降低子宫和卵巢质量、子宫指数和卵巢指数(P < 0.01)，加减知柏地黄丸低剂量组可降低子宫质量增加及子宫指数和卵巢指数(P < 0.05)；加减知柏地黄丸低剂量组及甲地孕酮组均有抑制抑那通降低E2水平的作用(P < 0.05，P < 0.01)，各给药组对LH水平、诱导阴道角化细胞、排卵后出现的子宫内膜分泌期改变无明显影响。结论 加减知柏地黄丸可拮抗抑那通刺激诱导的ICPP，其机制可能是通过抑制下丘脑-垂体-性腺轴(HPGA)的功能起作用。

Objective To observe the effect of modified Zhibo Dihuang Pills(MZDP) on counteracting Leuprorelin in inducing mice idiopathic central precocious puberty(ICPP). Methods Fifty BALB/c female mice aged 18 days were randomized into 5 groups:normal group，model group，high- and low- dose MZDP groups，and megestrol acetate group. The mice in the normal group received intramuscular injection of saline and intragastric administration of distilled water，the mice in other groups received the intramscular injection of Leuprorelin，a gonadotropin-releasing hormone analogue(GnRH-A) to establish ICPP model，and then were given the corresponding drugs by intragastric administration. After treatment，the vaginal opening，body weight，uterine weight and ovarian weight as well as the serum levels of luteinizing hormone(LH) and estrogen(E2) were detected. Meanwhile，the uterus index and ovaries index were examined，and ovarian histopathology was examined by vagina and cervix exfoliated cell smear. Results High-dose or low-dose MZDP had inhibition on the advance of vaginal opening in ICPP mice from modeling day 2-6 or 2-4(P < 0.05 or P < 0.01 compared with the model group)，while megestrol acetate had the same effect on ICPP mice from modeling day 3. Compared with the model group，high-dose MZDP and megestrol acetate decreased the weight of uterus and ovaries，and inhibited the rise of uterus index and ovaries index(P < 0.01)，low-dose MZDP decreased the uterine weight and inhibited the rise of uterus index and ovaries index(P < 0.05). Low-dose MZDP and megestrol acetate counteracted the decrease of serum E2 level of ICPP mice(P < 0.05 or P < 0.01). All of the medication groups had no effect on the increase of serum LH level and the formation of vaginal keratinocytese，and post-ovulation endometrial secretory phase of Leuprorelin-induced ICPP mice. Conclusion MZDP can antagonize Leuprorelin- induced ICPP，and the mechanism is probably related with the inhibition of the function of hypothalamic-pituitary- gonad axis.

R285.5

广东省中医药管理局项目(101039)。