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孙艳艳 俞建 时毓民 汪永红 李静 田占庄
（复旦大学儿科医院，复旦大学医学院）
Effects of Chinese Herbal Mixture on the Expression of Hypothalamic Ghrelin and Its Receptor in Female
Precocious Rats Induced by Danazol
Sun Yanyan1, Yu Jian1#, Shi Yumin1, Wang Yonghong1, Li Jing2, Tian ZhanZhuang2
（1 Children’s Hospital of Fudan University, Shanghai, China 2Shanghai Medical College of Fudan University,
Shanghai, China #Coresponding Author: Yu Jian, yuj@shmu.edu.cn）
Abstract To investigate the gene expression of hypothalamic Ghrelin/GHSR1-a during puberty onset, female
precocious rat models were induced by Danazol，a synthetic steroid ethisterone, and administrated with a Chinese
herbal mixture to observe its influence on hypothalamic Ghrelin and GHSR1-a gene expression.
第九届世界中医药大会
The 9th World Congress of Chinese Medicine
·245·
实 验 研 究
Experimental study
40 female SD rats aged 3 days were divided randomly into N group (normal control), M group(Danazol induced
precocious puberty model), TCM group(models fed with Chinese herbal mixture) and MS group (models fed
normal saline), 10 rats in each group. All the rats except those in N group were subcutaneously injected with
300μg Danazol to induce precocious puberty on postnatal day 5(P5). From P15, animals in TCM and MS were
administrated with Chinese Herbal Mixture and normal saline respectively. The samples in all groups were
collected provided the vulvas of the rats opened in M group. The results showed that E2 (19.97±2.62 pg/ml) ,
LH(16.96±1.31mIU/ml), hypothalamic GnRH (18.15±3.67pg/ml)and uterus organ index (49.71±5.50) in TCM
group were statistically lower than those in M (24.67±4.05 pg/ml,69.34±9.60,18.83±1.11 mIU/ml, 23.81±3.99
pg/ml)and MS (24.11±2.52 pg/ml,18.81±1.08 mIU/ml,66.53±6.87,22.70±2.52 pg/ml) (P<0.05), and the rats in
TCM group possessed a smaller ovary organ index compared with the ones in MS and N group.The levels of
Leptin, Ghrelin and IGF-1 were 6.74±0.83 ng/ml, 67.08±16.17 ng/mg, and 262.60±28.77 ng/ml respectively,
compared with those in M (7.10±1.05 ng/ml, 70.36±13.82 ng/ml, 250.04±31.97 ng/ml) and MS (7.13±1.17 ng/ml,
82.70±16.56 ng/ml, 256.62±31.84 ng/ml) (P>0.05), and there were no statistic correlation between the indices
related puberty onset and indices related to energy metabolism among all groups(P>0.05). There were lower
levels of hypothalamic Ghrelin and GHSR1-a mRNA in M (0.82±0.03, 0.91±0.05) and MS (0.87±0.03, 0.88± 0.03)
in comparison to those in the N group (1.00±0.02, 1.00±0.05）（P<0.01), The levels of hypothalamic Ghrelin and
GHSR1-a mRNA in TCM group(0.96±0.05, 1.00±0.02) were statistically higher than those in M and MS (P<0.01).
The rats exposed to Danazol on postnatal 5 days exhibited an increase in hypothalamic Ghrelin and GHSR1-a
mRNA when they developed early puberty onset. The Chinese Herbs could up-regulate the gene transcription of
hypothalamic Ghrelin and GHSR1-a, which might be an approach to delay the puberty onset.
（复旦大学儿科医院，复旦大学医学院）
Effects of Chinese Herbal Mixture on the Expression of Hypothalamic Ghrelin and Its Receptor in Female
Precocious Rats Induced by Danazol
Sun Yanyan1, Yu Jian1#, Shi Yumin1, Wang Yonghong1, Li Jing2, Tian ZhanZhuang2
（1 Children’s Hospital of Fudan University, Shanghai, China 2Shanghai Medical College of Fudan University,
Shanghai, China #Coresponding Author: Yu Jian, yuj@shmu.edu.cn）
Abstract To investigate the gene expression of hypothalamic Ghrelin/GHSR1-a during puberty onset, female
precocious rat models were induced by Danazol，a synthetic steroid ethisterone, and administrated with a Chinese
herbal mixture to observe its influence on hypothalamic Ghrelin and GHSR1-a gene expression.
第九届世界中医药大会
The 9th World Congress of Chinese Medicine
·245·
实 验 研 究
Experimental study
40 female SD rats aged 3 days were divided randomly into N group (normal control), M group(Danazol induced
precocious puberty model), TCM group(models fed with Chinese herbal mixture) and MS group (models fed
normal saline), 10 rats in each group. All the rats except those in N group were subcutaneously injected with
300μg Danazol to induce precocious puberty on postnatal day 5(P5). From P15, animals in TCM and MS were
administrated with Chinese Herbal Mixture and normal saline respectively. The samples in all groups were
collected provided the vulvas of the rats opened in M group. The results showed that E2 (19.97±2.62 pg/ml) ,
LH(16.96±1.31mIU/ml), hypothalamic GnRH (18.15±3.67pg/ml)and uterus organ index (49.71±5.50) in TCM
group were statistically lower than those in M (24.67±4.05 pg/ml,69.34±9.60,18.83±1.11 mIU/ml, 23.81±3.99
pg/ml)and MS (24.11±2.52 pg/ml,18.81±1.08 mIU/ml,66.53±6.87,22.70±2.52 pg/ml) (P<0.05), and the rats in
TCM group possessed a smaller ovary organ index compared with the ones in MS and N group.The levels of
Leptin, Ghrelin and IGF-1 were 6.74±0.83 ng/ml, 67.08±16.17 ng/mg, and 262.60±28.77 ng/ml respectively,
compared with those in M (7.10±1.05 ng/ml, 70.36±13.82 ng/ml, 250.04±31.97 ng/ml) and MS (7.13±1.17 ng/ml,
82.70±16.56 ng/ml, 256.62±31.84 ng/ml) (P>0.05), and there were no statistic correlation between the indices
related puberty onset and indices related to energy metabolism among all groups(P>0.05). There were lower
levels of hypothalamic Ghrelin and GHSR1-a mRNA in M (0.82±0.03, 0.91±0.05) and MS (0.87±0.03, 0.88± 0.03)
in comparison to those in the N group (1.00±0.02, 1.00±0.05）（P<0.01), The levels of hypothalamic Ghrelin and
GHSR1-a mRNA in TCM group(0.96±0.05, 1.00±0.02) were statistically higher than those in M and MS (P<0.01).
The rats exposed to Danazol on postnatal 5 days exhibited an increase in hypothalamic Ghrelin and GHSR1-a
mRNA when they developed early puberty onset. The Chinese Herbs could up-regulate the gene transcription of
hypothalamic Ghrelin and GHSR1-a, which might be an approach to delay the puberty onset.
