知柏地黄丸对瘦素诱导特发性性早熟模型小鼠的影响

Effect of Zhibo Dihuang Pill on Leptin-induced Idiopathic Central Precocious Puberty in Mice

【目的】观察知柏地黄丸对瘦素（leptin）诱导的特发性中枢性性早熟（ICPP）模型小鼠的影响。【方法】选用18日龄BALB/c雌性小鼠,随机分为6组：正常对照组,ICPP模型组,知柏地黄丸高、低剂量组（剂量分别为101.4、50.7.gkg-1.d-1）,甲地孕酮对照组（剂量为3.9 mg· kg^-1· d^-1）,促性腺激素释放激素类似物（GnRH-A）组（首次剂量为1 573.5μg/kg,第2、3次剂量均为1 180μg/kg,隔日1次;除正常对照组外,其他各组均腹腔注射leptin（20 mg/kg）复制模型;检测各组小鼠阴道开口数,体质量,子宫、卵巢质量及血清黄体生成素（LH）、雌二醇（E2）含量,并计算子宫与卵巢指数。【结果】知柏地黄丸高剂量组于造模第4-6天对leptin所致阴道开口提前有抑制作用（均P〈0.05或P〈0.01）;知柏地黄丸低剂量组可降低模型小鼠的子宫质量,抑制leptin所致子宫指数与卵巢指数升高（均P〈0.05或P〈0.01）;知柏地黄丸高、低剂量组可降低模型小鼠的LH水平（均P〈0.01）,但对模型小鼠的体质量及血清E2水平无显著影响（均P〉0.05）。【结论】知柏地黄丸治疗ICPP的作用可能与其能抑制下丘脑—垂体—性腺轴的提前发动有关。

Objective To observe the effect of Zhibo Dihuang Pill （ZDP） on leptin-induced idiopathic central precocious puberty （ICPP） in mice. Methods Eighteen BALB/c female mice aged 18 months were randomized into 6 groups： normal group, model group, high-and low-dose ZDP groups （at the dose of 101.4 and 50.7 g· kg^-1· d^-1respectively）, and megestrol acetate （3.9 mg· kg^-1· d^-1） group and gonadotropin releasing hormone analogues （GnRH-A） group （at the first dose of 1573.5 μg/kg, the second and the third dose of 1180 μg/kg, once every other day）. Except the normal group, the mice in other groups received intraperitoneal injection of leptin 20mg/kg to establish ICPP model. After treatment, the vaginal opening, body weight, uterus weight and ovaries weight as well as the serum levels of luteinizing hormone （ LH）, estrogen （ E2 ） were detected. Meanwhile, the uterus index and ovaries index were also examined. Results High-dose ZDP had an inhibition on the advance of vaginal opening induced by leptin after modeling for 4 -6 days （P 〈 0. 05 or P 〈 0. 01 compared with the model group）. Low-dose ZDP decreased the uterus weight, and inhibited the leptin-induced rise of uterus index and ovaries index （P 〈 0. 05 or P 〈 0. 01 compared with the model group）. High-and low-dose ZDP decreased LH level of ICPP mice （P 〈0.01 compared with the model group）, but had no effect on body weight and serum E2 level （P 〉 0. 05 ）. Conclusion The therapeutic effect of ZDP for ICPP is probably related with the inhibition of the advance of hypothalamic-pituitary-gonad axis activation.