曲普瑞林治疗真性性早熟的中枢机制

Central mechanism of triptorelin therapeutic effects on female precocious puberty in rats

目的观察曲普瑞林对真性性早熟的治疗作用,并探讨其药理作用的中枢机制。方法雌性Sprague-Dawley大鼠36只,分为正常组、模型组和曲普瑞林组。模型组和曲普瑞林组动物5日龄时皮下注射达那唑300μg;曲普瑞林组在15日龄时开始给予曲普瑞林(50 g·100 g^(-1)体重)肌内注射,每3 wk一次,共2次。观察3组大鼠性周期和动物脏器系数,并采用逆转录聚合酶链式反应(RT-PCR)检测大鼠下丘脑神经肽Kisspeptin和G蛋白偶联受体54(GPR54)mRNA的表达。结果与正常组相比,模型组大鼠阴门开启及建立规律性周期时间均明显提前,卵巢和子宫的脏器系数也明显增加(P<0.05);和模型组相比,曲普瑞林组大鼠阴门开启及建立规律性周期时间均明显延迟,卵巢和子宫的脏器系数明显减小(P<0.05),而与正常组无明显差异(P>0.05)。模型组大鼠下丘脑Kisspeptin和GPR54mRNA的D值为(0.427±s 0.008)和(0.482±0.021),高于正常组[(0.266±0.029)和(0.31±0.03)]和曲普瑞林组[(0.332±0.019)和(0.33±0.03)](P<0.01),曲普瑞林组和正常组相比无明显差异(P>0.05)。结论曲普瑞林可抑制性早熟大鼠下丘脑-垂体-性腺轴的过早启动,其对下丘脑内:Kisspeptin/GPR54 mRNA表达的抑制可能是其中枢作用机制之一。

AIM To observe the central mechanism of the GnRH analog-triptorelin on the precocious puberty female rats induced by danazol, through the pharmacologic detection of the hypothalamic expression of Kisspeptin and its receptor G protein-coupled receptor 54 （GPRS4） were detected. METHODS Thirty-six female SD rats at 3 days of age fed in company with their mothers were randomly divided into normal group （N）, model group （M）, and model with triptorelin treatment group （M ＋ T）. The animals in M and M ＋ T at the postnatal 5th day were given a single dose （300μg） danazol by subcutaneous injection. At the postnatal 15th days, the rats in M ＋ T were treated by subcutaneous injection of triptorelin （50 g·100 g^-1 body weight） once per three weeks, totally for two times. From the postnatal 25th day, the days of the vaginal opening were recorded and the exfoliative vaginal epithelial cells were examined every day until the establishment of first estrus cycle. The organ coefficients of uterus and ovary in each group were observed. The expression of Kisspeptin/GPR54 mRNA was also detected by means of RT-PCR. RESULTS The days of vaginal opening and establishment of first estrus cycle were advanced, and the organ coefficients of uterus and ovary increased in M than those of N. The days of vaginal opening and the establishment of first estrus cycle were postponed, and the organ coefficients decreased in M ＋ T comparing with those of M, but showing no significant difference with N （P 〉 0.05）. The expressions of Kisspeptin and GPR54 mRNA in M （（0.427 ± s 0.008） and （0.482 ±0.021）） were higher than those in N （（0.266 ± 0.029） and （0.31 ± 0.03）） and M ＋ T （（0.332 ± 0.019） and （0.33 ± 0.03） ） （P 〈 0.01） , hut no obvious difference was found between M ＋ T and N （P 〉 0.05） . CONCLUSION Triptorelin might inhibit abnormal early startup of hypothalamus-pituitary-gonad axis of precocious puberty rats induced by danazo, to synthesis and release the expression of hypothalamic Kisspeptin/ GPR54 mRNA, and thus probably be one of the mechanisms.