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郑州大学 附属儿童医院,河南省儿童医院 郑州儿童医院,郑州 450053
Received:07 February 2022,
Published Online:21 June 2022,
Published:20 December 2022
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岳上赛,孙凤平.知柏地黄丸加减治疗特发性性早熟的疗效观察[J].中国实验方剂学杂志,2022,28(24):138-144.
YUE Shangsai,SUN Fengping.Efficacy of Modified Zhibai Dihuangwan on Idiopathic Precocious Puberty[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(24):138-144.
岳上赛,孙凤平.知柏地黄丸加减治疗特发性性早熟的疗效观察[J].中国实验方剂学杂志,2022,28(24):138-144. DOI: 10.13422/j.cnki.syfjx.20221622.
YUE Shangsai,SUN Fengping.Efficacy of Modified Zhibai Dihuangwan on Idiopathic Precocious Puberty[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(24):138-144. DOI: 10.13422/j.cnki.syfjx.20221622.
目的
2
评价知柏地黄丸加减治疗特发性性早熟(ICPP)女性患儿的临床疗效及探讨其可能的作用机制。
方法
2
收集河南省儿童医院自2019年7月至2020年7月收治的ICPP女性患儿共78例,按随机信封法分为观察组和对照组,各39例。观察组给予知柏地黄丸加减治疗(1剂/d,分2次口服),对照组给予知柏地黄汤治疗(1剂/d,分2次口服),治疗周期3月。观察两组治疗前后乳核长径、最大卵泡直径、子宫、卵巢容积的变化情况及检测两组血清黄体生成素(LH)、卵泡刺激素(FSH)、催乳素(PRL)、雌激素(E
2
)水平;在细胞水平上,检测知柏地黄丸加减与传统知柏地黄汤2种不同方药处理后下丘脑GT1-7细胞促性腺激素释放激素(GnRH)的分泌量及性早熟相关基因亲吻素-1(Kiss-1)、G蛋白偶联受体54(GPR54)mRNA的表达水平。
结果
2
与本组治疗前比较,两组患儿治疗后血清性激素水平均显著下降(
P
<
0.01);治疗后,与对照组比较,观察组患儿乳核长径、最大卵泡直径明显缩小(
P
<
0.01);观察组临床有效率优于对照组(
P
<
0.01);细胞水平上,与传统知柏地黄汤组比较,知柏地黄丸加减组GT1-7细胞GnRH、Kiss-1、GPR54 mRNA表达水平明显降低。
结论
2
知柏地黄丸加减能有效抑制ICPP患儿血清性激素水平,延缓性早熟患儿乳核及卵巢发育,较传统知柏地黄汤效果更明显,值得临床推广;抑制Kiss-1和GPR54 mRNA的表达水平可能是其治疗性早熟的作用机制之一。
Objective
2
To evaluate the clinical efficacy of modified Zhibai Dihuangwan on children (female) with idiopathic precocious puberty (ICPP) and to explore the mechanism.
Method
2
A total of 78 children with ICPP who were treated in Henan Children's Hospital from July 2019 to July 2020 were randomized into the observation group and control group by sealed envelope randomization with 39 in either group. The observation group was given modified Zhibai Dihuangwan (1 dose/day, oral, divided into two times) and the control group Zhibai Dihuangtang (1 dose/day, oral, divided into two times orally). The treatment lasted 3 months for both groups. The changes of mammary nucleus length, maximum follicular diameter, uterus, and ovarian volume before and after treatment in the two groups were observed, and serum luteinizing hormone (LH) level, follicle-stimulating hormone (FSH) level, prolactin (PRL) level, and estrogen (E
2
) level were detected in the two groups. At the cellular level, the secretion of gonadotropin releasing hormone (GnRH) and mRNA expression of precocious puberty-related genes Kiss-1 and G protein-coupled receptor 54 (GPR54) were measured.
Result
2
Levels of serum sex hormones of the two groups were significantly decreased after treatment as compared with those before treatment (
P
<
0.01). After treatment, the length of the mammary nucleus and the maximum follicular diameter in the observation group were smaller than those in the control group (
P
<
0.01). The total clinical effective rate in the observation group was higher than that in the control group (
P
<
0.01). At the cellular level, the expression levels of GnRH, Kiss-1 and GPR54 mRNA in GT1-7 cells treated with modified Zhibai Dihuangwan were lower than those treated with traditional Zhibai Dihuangtang.
Conclusion
2
Modified Zhibai Dihuangwan can effectively inhibit levels of serum sex hormones in children with ICPP and delay the development of mammary nucleus and ovary in children with precocious puberty. It is more effective than traditional Zhibai Dihuangtang, which is worthy of clinical promotion. The mechanism is the likelihood that it inhibits the expression of Kiss-1 and GPR54 mRNA.
BRITO V N , SPINOLA-CASTRO A M , KOCHI C , et al . Central precocious puberty revisiting the diagnosis and therapeutic management [J]. Arch Endocrinol Metab , 2016 , 60 ( 2 ): 163 - 172 .
TUNG Y C . Central precocious puberty in girls:Increasing with time [J]. Pediatr Neonatol , 2021 , 62 ( 2 ): 127 - 128 .
GANGAT M , RADOVICK S . Precocious puberty [J]. Minerva Pediatr , 2020 , 72 ( 6 ): 491 - 500 .
LEE M H , KIM S H , OH M , et al . Age at menarche in Korean adolescents:Trends and influencing factors [J]. Reprod Health , 2016 , doi: 10.1186/s12978-016-0240-y http://dx.doi.org/10.1186/s12978-016-0240-y .
ZHAO L , ZHONG Y . Effects of central precocious puberty on physical and sexual development in children [J]. Zhongguo Dang Dai Er Ke Za Zhi , 2014 , 16 ( 5 ): 555 - 559 .
王卫平 , 毛荫 , 李廷玉 , 等 . 儿科学 [M]. 第八版.北京 : 人民卫生出版社 , 2016 : 426 - 429
PETER H . Commentary: Cognitive,emotional,and psychosocial functioning of girls treated with pharmacological puberty blockage for idiopathic central precocious puberty [J]. Front Psychol , 2017 , doi: 10.3389/fpsyg http://dx.doi.org/10.3389/fpsyg .
DE SANCTIS V , SOLIMAN A T , DI MAIO S , et al . Long-term effects and significant adverse drug reactions (ADRs) associated with the use of gonadotropin-releasing hormone analogs (GnRHa) for central precocious puberty:A brief review of literature [J]. Acta Biomed , 2019 , 90 ( 3 ): 345 - 359 .
VURALLI D , GONC N E , OZON Z A , et al . Which parameters predict the beneficial effect of GnRHa treatment on height in girls with central precocious puberty [J]. Clin Endocrinol (Oxf) , 2021 , doi: 10.1111/cen.14420 http://dx.doi.org/10.1111/cen.14420 .
SUN W , HAN X , WANG Y , et al . Effectiveness of ZiYin Xiehuo granules and Zishen Qinggan granules on partial precocious puberty in girls: A multicenter, randomized, single-blind, controlled trial [J]. J Tradit Chin Med , 2018 , 38 ( 5 ): 740 - 745 .
LIN Y C , CHANG T T , CHEN H J , et al . Characteristics of traditional Chinese medicine usage in children with precocious puberty:A nationwide population-based study [J]. J Ethnopharmacol , 2017 , 205 : 231 - 239 .
林甦 , 杨文庆 , 俞建 . 中医儿科临床诊疗指南·性早熟(修订) [J]. 中医儿科杂志 , 2016 , 12 ( 13 ): 1 - 5 .
孙凤平 , 韩雪 , 葛国岚 . 知柏地黄丸化裁方治疗特发性性早熟疗效观察 [J]. 中医药学报 , 2018 , 46 ( 2 ): 86 - 89 .
KERMATH B A , GORE A C . Neuroendocrine control of the transition to reproductive senescence: lessons learned from the female rodent model [J]. Neuroendocrinology , 2012 , 96 ( 1 ): 1 - 12 .
LOSA-WARD S M , TODD K L , MCCAFFREY K A , et al . Disrupted organization of rfamide pathways in the hypothalamus is associated with advanced puberty in female rats neonatally exposed to bisphenol A [J]. Biol Reprod , 2012 , 87 ( 2 ): 28 .
中华医学会儿科学分会内分泌遗传代谢学组 . 中枢性性早熟诊断与治疗共识(2015) [J]. 中华儿科杂志 , 2015 , 53 ( 6 ): 412 - 417 .
颜纯 , 王慕逖 . 小儿内分泌学 [M]. 2 版. 北京 : 人民卫生出版社 , 2006: 316 - 317 .
郑筱萸 . 中药新药临床研究指导原则 [M]. 北京 : 中国医药科技出版社 , 2002 : 366 - 388 .
国家中医药管理局 . 中医病证诊断疗效标准 [M]. 北京 : 中国医药科技出版社 , 2012 : 234 .
任娟 , 李辉 , 叶进 . 单纯乳房早发育的中医药治疗现状 [J]. 中医儿科杂志 , 2019 , 15 ( 6 ): 113 - 116 .
李珊珊 , 赵芮莹 , 佟庆 . 柴嵩岩诊治小儿性早熟经验 [J]. 中国中医药信息杂志 , 2019 , 26 ( 5 ): 124 - 125 .
杨文庆 , 李淑闽 , 林甦 , 等 . 女童特发性中枢性性早熟中医证素特点研究 [J]. 中国中西医结合杂志 , 2020 , 40 ( 1 ): 31 - 34 .
郭春彦 , 张萌 , 柳静 , 等 . 基于文献的中药治疗女童性早熟用药规律研究 [J]. 中国医药导报 , 2021 , 18 ( 15 ): 167 - 170 .
梁博程 , 史晓林 , 许超 , 等 . 基于中药系统药理学方法研究六味地黄丸治疗骨质疏松症的药效成分、作用靶点及作用特点 [J]. 中医正骨 , 2019 , 31 ( 4 ): 1 - 7 .
TANG R , DING X , ZHU J . Kisspeptin and polycystic ovary syndrome [J]. Front Endocrinol , 2019 , doi: 10.3389/fendo http://dx.doi.org/10.3389/fendo .
OSUKA S , NAKANISHI N , MURASE T , et al . Animal models of polycytic ovary syndrome:A review of hormone-induced rodent models focused on hypothalamus-pituitary-ovary [J]. Reprod Med Biol , 2018 , 18 ( 2 ): 151 - 160 .
LEON S , BARROSO A , VAZQUEZ M J , et al . Direct actions of kisspeptins on GnRH neurons permit attainment of fertility but are insufficient to fully preserve gonadotropic axis activity [J]. Sci Rep , 2016 , doi: 10.1038/srep19206 http://dx.doi.org/10.1038/srep19206 .
SON Y L , UBUKA T , SOGA T , et al . Inhibitory action of gonadotropin-inhibitory hormone on the signaling pathways induced by kisspeptide in GnRH neuronal cell line, GT1-7 [J]. FASEB J , 2016 , 30 ( 6 ): 2198 - 2210 .
CHASON R J , KANG J H , GERKOWICZ S A , et al . GnRH agonist reduces estrogen receptor dimerization in GT1-7 cells: Evidence for cross-talk between membrane-initiated estrogen and GnRH signaling [J]. Mol Cell Endocrinol , 2015 , 404 : 67 - 74 .
FICHNA P , FICHNA M , ZURAWE K , et al . Hypogonadotropic hypogonadism due to GnRH receptor mutation in a sibling [J]. Endokrynol Pol , 2011 , 62 ( 3 ): 264 - 267 .
LEE S H , KWAK S C , KIM D K , et al . Effects of Huang Bai (Phellodendri Cortex) and three other herbs on GnRH and GH levels in GT1-7 and GH3 cells [J]. Evid Based Complement Alternat Med , 2016 ,10.1155/2016/9389028..
CHENG M , YE X D , MIAO Y P , et al . Experimental study on therapeutic effect of Dabuyin Wan on true precocious puberty in female rats [J]. Chin J Chin Mater Med , 2013 , 38 ( 3 ): 386 - 390 .
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