补肾中药对下丘脑-垂体促性腺机能的影响

目的:研究补肾中药对下丘脑促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)合成、分泌及其相关神经递质、神经肽的影响,探讨补肾中药调节下丘脑-垂体促性腺机能的作用环节和作用机制.方法:以正常青春启动期雌性SD大鼠(体重160～180 g,月龄1.5月)为实验动物模型,随机分为3组,分别喂饲生理盐水、滋阴泻火中药合剂和益肾填精中药合剂,灌胃法喂饲1次/d,剂量5 ml,共30 d.采用免疫组织化学及计算机图像处理技术对下丘脑内侧视前区、弓状核和正中隆起3处的GnRH和神经肽Y(neuropeptide Y,NPY)进行定量形态观察;采用组织匀浆法和放射免疫法测定下丘脑视前区GnRH含量;采用脑片孵育实验和高效液相色谱法测定内侧基底下丘脑单胺类递质的释放量;采用推挽灌流技术及放射免疫法测定下丘脑视前区GnRH 和NPY的释放量,高效液相色谱法测定该部位单胺类递质的释放量.结果:滋阴泻火中药可以显著抑制下丘脑GnRH周期性分泌中心及紧张性分泌中心GnRH的合成与释放,而益肾填精中药则显著促进其合成与释放.滋阴泻火中药可能通过抑制下丘脑GnRH紧张性分泌中心去甲肾上腺素的释放,促进下丘脑GnRH周期性分泌中心多巴胺的释放,及同时促进这两个GnRH分泌中心NPY的合成和释放,使下丘脑GnRH神经元的功能活动显著降低,从而明显抑制下丘脑-垂体的促性腺机能.益肾填精中药则可能通过降低下丘脑GnRH 紧张性分泌中心NPY的合成和释放,使GnRH神经元功能显著活跃,从而明显促进下丘脑-垂体的促性腺机能.结论:补肾中药可能通过对下丘脑GnRH及其相关神经递质去甲肾上腺素、多巴胺和NPY的合成与释放的调节作用,调整下丘脑-垂体的促性腺机能.

Effects of kidney-tonifying Chinese herbal medicine on hypothalamic-pituitary gonadotrophic function

OBJECTIVE: To observe the effects of kidney-tonifying Chinese herbal medicine on the synthesis and secretion of gonadotropin releasing hormone (GnRH) and the related neurotransmitters and neuropeptides, and to explore the mechanism of the regulative effect of Chinese herbal medicine on the hypothalamic-pituitary gonadotrophic function. METHODS: Female Sprague-Dawley rats during the period of normal adolescent initiation (160-180 g, 1.5 months) were randomly divided into three groups. The control group was fed with normal saline and the two experimental groups were fed with Chinese herbal medicine for nourishing yin to reduce fire (Zi Yin Xie Huo, ZYXH) or nourishing kidney to replenish essence (Yi Shen Tian Jing, YSTJ) respectively. The dosage was 5 ml/d for 30 days by gastric gavage. Integrated optic densities of the GnRH and neuropeptide Y (NPY) in medial preoptic area (MPOA), arcuate nucleus (ARC) and median eminence (ME) of hypothalamus were determined by immunohistochemistry method and image processing. The content of GnRH in homogenate of hypothalamus preoptic area was determined by radioimmunoassay (RIA). The releasing amount of monoamine neurotransmitters from medial basal hypothalamus (MBH) was determined by brain slices incubation and high pressure liquid chromatography (HPLC). The releasing amount of GnRH and NPY from POA was determined by push-pull perfusion and RIA, and the releasing amount of monoamine neurotransmitters from this site was determined by HPLC. RESULTS: ZYXH could inhibit the synthesis and secretion of GnRH from periodic and tonic secretory centers of GnRH, while YSTJ could stimulate the synthesis and secretion of GnRH from the both secretory centers of GnRH. ZYXH could inhibit the activity of GnRH neurons via diminishing the releasing of norepinephrine (NE) from tonic secretory center of GnRH, increasing the releasing of dopamine (DA) in periodic secretory center of GnRH and increasing the synthesis and releasing of NPY from the both secretory centers of GnRH, it hence inhibited the hypothalamic-pituitary gonadotrophic function. YSTJ could stimulate the activity of GnRH neurons via diminishing the synthesis and releasing of NPY from tonic secretory center of GnRH, it hence promoted the hypothalamic-pituitary gonadotrophic function. CONCLUSION: Chinese herbal medicine for tonifying the kidney could modulate hypothalamic-pituitary gonadotrophic function via regulating the synthesis and secretion of GnRH and the related neurotransmitters (NE, DA) and neuropeptides (NPY).