黄艳霞 刘建忠 张雪荣

〔摘要〕 目的 應用N-甲基-DL-天冬氨酸（NMA）构建SD雌性大鼠中枢性性早熟模型，并探讨九味楮实颗粒对雌性真性性早熟大鼠体质量及垂体分泌的卵泡刺激素（follicule-stimulating hormone， FSH）、促黄体生成素（luteinizing hormone， LH）、雌二醇（estradiol， E2）水平的影响。方法 选取48只26日龄SD雌鼠随机分对照组、模型组、西药组、中药高剂量组、中药中剂量组、中药低剂量组，每组8只。除对照组外，其余组均采用NMA方法建立性早熟动物模型，中药组、西药组分别予九味楮实颗粒、戈那瑞林干预，对照组和模型组给予等体积的生理盐水干预，每日观察阴道口开放情况，每间隔2 d测一次体质量，计算各组大鼠脏器系数（子宫、卵巢及双侧乳腺），采用ELISA检测血清FSH、LH、E2水平。结果 与对照组比较，模型组大鼠阴道口开放时间提前（P<0.05）;大鼠在出生后26、29、32 d体质量无明显变化（P>0.05）;子宫系数升高（P<0.05）;血清LH、FSH水平明显增加（P<0.05）。与模型组比较，西药组、中药各剂量组大鼠阴道口开放时间明显延迟（P<0.05）;中药高剂量组大鼠在出生后35、38 d体质量明显降低（P<0.05）;西药组、中药中剂量组大鼠子宫系数降低（P<0.05）;西药组、中药中剂量组大鼠卵巢系数及双侧乳腺系数无明显变化（P>0.05）;西药组、中药高剂量组、中剂量组的血清LH、FSH、E2水平明显降低（P<0.05）。与中药低剂量组比较，中药高中剂量组的血清LH、FSH、E2水平明显降低（P<0.05）。结论 九味楮实颗粒可抑制NMA诱发雌鼠性早熟的发生，同时能降低性早熟模型大鼠的血清LH、FSH、E2的水平，推测九味楮实颗粒可能通过调节下丘脑-垂体-性腺轴起到抑制性早熟的作用。

〔关键词〕 性早熟;九味楮实颗粒;N-甲基-DL-天冬氨酸;体质量;性激素;大鼠

〔中图分类号〕R285.5       〔文献标志码〕A       〔文章编号〕doi：10.3969/j.issn.1674-070X.2021.10.010

Effect of Jiuwei Chushi Granule on Body Mass and Sex Hormone Levels of Central

Precocious Puberty in SD Female Rats

HUANG Yanxia1， LIU Jianzhong1，2*， ZHANG Xuerong1，2

（1. Hubei University of Chinese Medicine， Wuhan， Hubei 430065， China; 2. The Affiliated Hospital of Hubei

University of Chinese Medicine， Wuhan， Hubei 430061， China）

〔Abstract〕 Objective To construct a SD female rat model of central precocious puberty with N-methyl-DL-aspartate （NMA）， and to explore the effect of Jiuwei Chushi Granule on the body mass and the levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH） and estradiol （E2） secreted by pituitary gland. Methods 48 female SD rats at 26 days of age were randomly divided into control group， model group， western medicine group， high dose Chinese medicine group， medium dose Chinese medicine group and low dose Chinese medicine group， with 8 rats in each group. Except for the control group， the animal model of precocious puberty was established by NMA method in other groups. The Chinese medicine group and western medicine group were given Jiuwei Chushi Granule and gonadorelin intervention respectively. The control group and model group were given equal volume of normal saline intervention. The vaginal opening was observed daily， and the body weight was measured every two days. Organ coefficients （uterus， ovary and bilateral mammary gland） were calculated， and serum FSH， LH and E2 levels were detected by ELISA. Results Compared with the control group， the vaginal opening time of model group was earlier （P<0.05）; uterine coefficient increased （P<0.05）; serum LH and FSH levels were significantly increased （P<0.05）; there was no significant change in body weight of rats on day 26， 29 and 32 after birth （P>0.05）. Compared with model group， the opening time of vaginal opening in western medicine group and Chinese medicine groups was significantly delayed （P<0.05）; the body weight of rats in high dose Chinese medicine group was significantly decreased at 35 and 38 days after birth （P<0.05）; uterine coefficient of western medicine group and medium dose Chinese medicine group decreased （P<0.05）; there were no significant changes in ovarian coefficient and bilateral mammary gland coefficient in western medicine group and medium dose Chinese medicine group （P>0.05）; serum LH， FSH and E2 levels in western medicine group， high dose Chinese medicine group and medium dose Chinese medicine group were significantly decreased （P<0.05）. Compared with the low dose Chinese medicine group， the levels of LH， FSH and E2 in the high dose Chinese medicine group and medium dose Chinese medicine group were significantly decreased （P<0.05）. Conclusion Jiuwei Chushi Granule can inhibit NMA induced precocious puberty in female rats and reduce the levels of serum LH， FSH， E2 in precocious rats. Jiuwei Chushi Granule may inhibit precocious puberty by regulating hypothalamus-pituitary-gonadal axis.

〔Keywords〕  precocious puberty; Jiuwei Chushi Granule; N-methyl-DL-aspartate; body mass; sex hormone; rat

性早熟[1]是指女孩在8岁之前、男孩在9岁之前出现性发育征象，是由GnRH神经元的过早激活引起的[2]，是小儿常见的内分泌疾病之一。根据下丘脑-垂体-性腺轴功能启动与否，又分为真性性早熟和假性性早熟，而真性性早熟以中枢性性早熟最常见[1]。据报道全球性早熟发病率约为0.2%，女孩是男孩的5～10倍，性早熟已成为全球关注的热点问题，若性早熟患儿得不到及时正确治疗，会引起骨骺端提前闭合，致终身高矮小及一系列心理行为问题[3]。目前，治疗性早熟常用的西药为促性腺激素释放激素类似物，但其价格昂贵，长期使用会给患儿家庭带来沉重经济负担，而诸多文献[4-7]证明中医药治疗性早熟已取得良好效果。……