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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。
Objective To observe the therapeutic effect of triptorelin on true precocious puberty and to explore the central mechanism of its pharmacological effects. Methods Thirty-six female Sprague-Dawley rats were divided into normal group, model group and triptorelin group. The model group and the triptorelin group were subcutaneously injected with 300μg of danazol at 5 days of age. The triptorelin group (50 g · 100 g -1 body weight) at the age of 15 days Intra-injection, once every 3 weeks, 2 times in total. The sexual cycle and animal organ coefficient of the rats in the three groups were observed. The expression of kisspeptin and G protein-coupled receptor 54 (GPR54) mRNA of rat hypothalamus was detected by reverse transcription polymerase chain reaction (RT-PCR). Results Compared with the normal group, the opening of the vulva and the regular cycle time of the model rats were significantly advanced and the organ coefficients of ovary and uterus were significantly increased (P <0.05). Compared with the model group, the triptorelin group The opening of the vulva in rats and the establishment of the regular cycle time were significantly delayed, ovarian and uterine organ coefficient was significantly reduced (P <0.05), but no significant difference with the normal group (P> 0.05). The D values of hypothalamus Kisspeptin and GPR54 mRNA in model group were (0.427 ± s 0.008) and (0.482 ± 0.021), respectively, higher than those in normal group [(0.266 ± 0.029) and (0.31 ± 0.03)] and triptorelin group (0.332 ± 0.019) and (0.33 ± 0.03), respectively (P <0.01). There was no significant difference between triptorelin group and normal group (P> 0.05). Conclusion Triptorelin can inhibit the premature start of the hypothalamic-pituitary-gonadal axis in precocious rats. Inhibition of Kisspeptin / GPR54 mRNA expression in the hypothalamus may be one of its central mechanisms.