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目的:探讨复方地黄合剂联合生长激素(rhGH)对青春期大鼠性发育及生长的调控作用。方法:将SPF级4周龄雌性SD大鼠随机分为正常组、中药组、rhGH组和联合组,分别予生理盐水或相应药物干预。每天观察实验动物阴道口开放(VO)时间;干预2周后计算子宫、卵巢指数及胫骨长度;Real-time荧光定量PCR法检测下丘脑组织KiSS-1、GPR54、Ghrelin mRNA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。结果:中药组与联合干预组大鼠VO时间均较单用rhGH明显推后(P<0.05),且联合干预组大鼠胫骨长度较中药组显著增加(P<0.05)。中药组大鼠子宫卵巢脏器指数明显降低,加用rhGH联合干预后子宫、卵巢指数未见明显增加(P>0.05)。中药组下丘脑KiSS-1、GPR 54 mRNA表达均降低,而rhGH组KiSS-1、GPR54 mRNA表达明显增高(P<0.01),联合干预后亦呈降低趋势;Ghrelin mRNA表达各组之间比较差异无统计学意义(P>0.05)。中药组血清LH、FSH、Ghrelin较正常组均明显降低(P<0.01),而rhGH组均明显升高(P<0.01),联合组干预后亦呈明显降低趋势(P<0.01);血清IGF-1各组之间没有显著性差异(P>0.05)。结论:复方地黄合剂可以抑制KiSS-1、GPR54基因表达,调控外周FSH、LH激素水平,抑制性发育,配合生长激素可以有效增加动物体长,二者合用可达到控制性早熟和改善终身高的效果。
Aims: To investigate the regulation of rhGH on sexual development and growth of adolescent rats. Methods: SPF 4-week-old female Sprague-Dawley rats were randomly divided into normal group, traditional Chinese medicine group, rhGH group and combined group, respectively, with saline or corresponding drug intervention. The vaginal opening (VO) of the experimental animals was observed every day. The uterine and ovarian index and the length of the tibia were calculated 2 weeks after the intervention. The expressions of KiSS-1, GPR54 and Ghrelin mRNA in the hypothalamus were detected by Real-time fluorescent quantitative PCR. Serum FSH, LH, Ghrelin and IGF-1 expression. Results: Compared with rhGH alone, the VO time in the Chinese medicine group and the combined intervention group was significantly delayed (P <0.05), and the length of the tibia in the intervention group was significantly higher than that in the traditional Chinese medicine group (P <0.05). The uterus ovary index of the rats in the TCM group was significantly lower, but the uterus and ovary index did not increase significantly with rhGH intervention (P> 0.05). The expressions of KiSS-1 and GPR 54 mRNA in the hypothalamus of Chinese medicine group were decreased, while the expressions of KiSS-1 and GPR54 mRNA in rhGH group were significantly increased (P <0.01), and also decreased with the intervention; the expression of Ghrelin mRNA was significantly different among groups No statistical significance (P> 0.05). Serum levels of LH, FSH and Ghrelin in the TCM group were significantly lower than those in the normal group (P <0.01), while those in the rhGH group were significantly increased (P <0.01), and also decreased in the combination group (P <0.01) There was no significant difference between groups (P> 0.05). CONCLUSION: Fufang Digu Mixture can inhibit the expression of KiSS-1 and GPR54 gene, regulate the level of FSH and LH, and inhibit the development of the body. Combined with growth hormone can effectively increase the body length of animals, and the combination of the two can achieve the control of precocious puberty and the improvement of the longevity effect.