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目的探讨中药复方地黄合剂对青春期大鼠性发育的调节作用及可能的作用机制。方法将16只SPF级4周龄SD雌性大鼠随机分为两组,正常组予0.9%NaCl溶液灌胃,中药组予复方地黄合剂灌胃。每天观察大鼠阴道口开放(VO)时间;干预2周后计算子宫、卵巢指数;Real-time荧光定量PCR法检测下丘脑组织KiSS-1及其GPR54和GhrelinmRNA的表达;ELISA法检测血清卵泡刺激素(FSH)、黄体生成素(LH)、Ghrelin以及胰岛素样生长因子-1(IGF-1)的表达浓度。结果中药组VO时间平均推迟约7d,子宫、卵巢指数较正常组均明显降低(P<0.01);中药组血清LH、Ghrelin均显著降低(P<0.01),而对FSH、IGF-1无明显影响(P>0.05);中药组KiSS-1、GPR54mRNA表达量分别降低至正常组的0.22和0.17倍,差异有显著性(P<0.01),而GhrelinmRNA变化不明显(P>0.05)。结论复方地黄合剂对青春期大鼠性发育有明显的调节作用,其作用机制可能与抑制KiSS-1、GPR54基因表达,从而影响外周FSH、LH等激素水平有关。
Objective To investigate the regulatory effect of traditional Chinese medicine Dihuang mixture on sexual development of adolescent rats and its possible mechanism. Methods Sixteen SPF 4-week-old female Sprague-Dawley rats were randomly divided into two groups. The rats in normal group were treated with 0.9% NaCl solution. The vaginal opening (VO) time of rats was observed every day. The uterus and ovary index were calculated after intervention for 2 weeks. The expression of KiSS-1, GPR54 and Ghrelin mRNA in hypothalamus were detected by Real-time fluorescent quantitative PCR. Serum follicle stimulation (FSH), luteinizing hormone (LH), Ghrelin and insulin-like growth factor-1 (IGF-1). Results The VO time of the Chinese medicine group was delayed by about 7 days on average, and the index of uterus and ovary of the Chinese medicine group was significantly lower than that of the normal group (P <0.01). Serum LH and Ghrelin were significantly decreased (P <0.01) (P> 0.05). The expressions of KiSS-1 and GPR54 mRNA in Chinese medicine group were reduced to 0.22 and 0.17 times of those in normal group (P <0.01), but the changes of Ghrelin mRNA were not significant (P> 0.05). Conclusions Compound Dihuang Mixture can obviously regulate the sexual development of adolescent rats. Its mechanism may be related to the inhibition of the expression of KiSS-1 and GPR54 genes and the influence of the levels of FSH and LH on peripheral hormones.