节点文献
中药调整性早熟儿童青春发育进程的机制研究
Effects of Chinese herbal medicine on modulating the course of puberty development in children with precocious puberty
【摘要】 目的:从神经内分泌调节及基因表达的角度,探讨调整性早熟儿童青春发育进程的滋阴泻火中药和益肾填精中药有效调节下丘脑垂体促性腺机能、促生长机能的作用机制。方法:青春期大鼠分别予以喂饲滋阴泻火中药或益肾填精中药。采用神经生物学实验方法(下丘脑推挽灌流、组织匀浆、脑片孵育及免疫组化法)检测下丘脑促性腺区促性腺激素释放激素(gonadotropinreleasinghormone,GnRH)的含量、脉冲释放频率与幅度,以及中枢氨基酸递质、神经肽Y及β内啡肽释放的变化;采用定量逆转录聚合酶链反应检测下丘脑GnRH、生长激素释放激素(growthhormonereleasinghormone,GHRH)、生长抑素(somatostatin,SS)、腺垂体卵泡刺激素(follicularstimulatinghormone,FSH)、黄体生成素(luteinizinghormone,LH)、生长激素(growthhormone,GH)、长骨干骺端胰岛素样生长因子Ⅰ(insulinlikegrowthfactorⅠ,IGFⅠ)基因及蛋白的表达水平。结果:滋阴泻火中药可明显抑制下丘脑促性腺区兴奋性氨基酸递质的释放,促进抑制性氨基酸递质、神经肽Y和β内啡肽的释放,使下丘脑GnRH神经元的功能活动降低,下调GnRH、FSH及LH基因的表达水平,上调下丘脑SS基因的表达,并下调垂体GH及长骨干骺端IGFⅠ基因的表达,从而明显抑制下丘脑垂体的促性腺机能及促生长机能。益肾填精中药则可明显抑制下丘脑促性腺区神经肽Y的释放,使下丘脑GnRH神经元的功能活跃,上调GnRH、FSH及LH基因的表达,下调下丘脑SS基因的表达,上调垂体GH及长骨干骺端IGFⅠ基因的表达,从而明显促进下丘脑垂体的促性腺机能及促生长机能。结论:滋阴泻火中药和益肾填精中药可通过调整机体的神经内分泌调节机制,调整下丘脑GnRH、SS,腺垂体FSH、LH、GH及长骨干骺端IGFⅠ基因的转录,有效调节下丘脑垂体的促性腺机能及促生长机能。这可能是滋阴泻火中药和益肾填精中药可有效调整性早熟患儿青春发育进程及改善骨骼发育的主要作用机制。
【Abstract】 Objective: To explore the therapeutic effects of Ziyin Xiehuo Recipe (ZYXHR) for nourishing yin and lowering fire and Yishen Tianjing Recipe (YSTJR) for nourishing kidney and replenishing essence on regulating the gonadotrophic and somatotrophic functions of hypothalamic-pituitary axis, and to reveal the mechanisms of ZYXHR and YSTJR in modulating the course of pubertal development of children with precocious puberty. Methods: The pubertal rats were fed with ZYXHR or YSTJR for 30 days, and the parameters of rats were monitored as the followings: The content of gonadotropin-releasing hormone(GnRH), the frequency and amplitude of GnRH impulse releasing, the releasing amounts of aminoacid neurotransmitters, and neuropeptide Y (NPY) and β-endorphin (β-END) in the gonadotrophic area of the hypothalamus were detected with neurobiological methods (push-pull perfusion, homogenate, incubation of brain slices, and immunohistochemical staining). The levels of gene and protein expressions of GnRH, growth hormone releasing hormone (GHRH) and somatostatin (SS) in hypothalamus, and follicular stimulating hormone (FSH), luteinizing hormone (LH) and growth hormone (GH) in adenohypophysis as well as insulin-like growth factorⅠ (IGF-Ⅰ) in metaphysis were determined with real time reverse transcription-polymerase chain reaction (RT-PCR). Results: The ZYXHR could reduce the activity of GnRH neurons in hypothalamus through inhibiting the release of central exciting aminoacid neurotransmitters, whereas promoting the release of central inhibiting aminoacid neurotransmitters, NPY and β-END in gonadotrophic area of hypothalamus. The expression levels of GnRH, FSH and LH mRNAs were down-regulated while the expression level of SS mRNA in hypothalamus was up- regulated in the ZYXHR-treated group. The GH mRNA in hypophysis and the IGF-Ⅰ mRNA in metaphysis were both down-regulated by ZYXHR. The YSTJR could promote the activity of GnRH neurons in hypothalamus through inhibiting the release of NPY in gonadotrophic area of hypothalamus, up- regulating the expression levels of GnRH, FSH, LH and GH mRNAs in hypophysis, and IGF-Ⅰ mRNA in metaphysis, while down-regulating the expression level of SS mRNA in hypothalamus. Conclusion: The ZYXHR and YSTJR could both regulate the gonadotrophic and somatotrophic functions of hypothalamic-pituitary axis through modulating the neuroendocrine regulation and the gene expressions of GnRH and SS in hypothalamus, GH, FSH and LH in hypophysis, and IGF-Ⅰ in metaphysis. These may be the chief mechanisms of ZYXHR and YSTJR in modulating the course of pubertal development and ameliorating the skeletal development in children with precocious puberty.
【Key words】 Chinese materia medica; puberty, precocious; neurotransmitters; neuropeptide Y; β-endorphin; hypothalamic-pituitary-gonadal axis; somatostatin-growth hormone-IGF-Ⅰ axis;
- 【文献出处】 中西医结合学报 ,Journal of Chinese Integrative Medicine , 编辑部邮箱 ,2006年02期
- 【分类号】R272
- 【被引频次】42
- 【下载频次】633