补骨脂颗粒对顺铂致小鼠卵巢损伤的保护作用
摘要
化疗作为主要抗癌治疗手段,对女性卵巢的结构、功能均可产生严重损害,造成卵巢早衰及相关不孕。因此,如何在肿瘤治疗的同时保存妇女的卵巢功能,有着巨大的医学需求,是一个值得研究的重要课题。西医方面一般情况下采用雌激素替代疗法(hormone replacement therapy, HRT),但增加了雌激素依赖性肿瘤的发病风险。植物雌激素则具有双向调节的作用,避免了HRT的高副作用,是安全性更高的治疗成分。基于中医理论,本实验室对多种具有滋肾益精,调和气血的中药进行筛选,发现这些中药有植物雌激素样的作用。补骨脂就是其中的一味。
此外,近年来补骨脂对于缓解化疗后副作用的研究也日渐趋多,主要是针对一些肾毒性,免疫功能退化等连锁效应。对于使用补骨脂颗粒对损伤的小鼠卵巢进行保护的实验研究很少。结合本实验室关于植物雌激素在妇科疾病的应用理论和研究经验,选用补骨脂颗粒对小鼠顺铂损伤的卵巢进行干预,观察其是否具有保护作用,并对临床用药提供新的依据和指导。
本课题针对补骨脂颗粒对顺铂损伤的卵巢的保护机制进行两个水平的研究：
1整体水平的研究
顺铂是具有细胞毒作用的非特异性药物,具有较强的广谱抗癌作用。同时具有强烈的肝肾毒性作用。补骨脂对其保护作用体现在整体方面。
1.1补骨脂颗粒不同剂量灌胃对顺铂损伤后小鼠形态和体重的影响
顺铂腹腔注射后的小鼠毛色灰暗且炸立,目光呆滞,蜷卧少动,饮食量下降,体重急剧减少。停止注射顺铂,体重都有所回升,但症状改善差别明显。补骨脂颗粒不同剂量灌胃后,小鼠的形态和体重恢复良好,程度不一。
1.2补骨脂颗粒不同剂量灌胃对小鼠肝、脾、肾脏器质量的影响
顺铂对肝、肾毒性作用研究较多,腹腔注射顺铂造成肝、肾、脾脏器的损伤,如质量下降,脏器系数降低的等。用药补骨脂颗粒后,小鼠各项脏器系数的值都较模型组高,尤其是肾脏系数值。这也表明了补骨脂的补肾护肾的作用。
1.3补骨脂颗粒不同剂量灌胃对小鼠卵巢和子宫质量和形态的影响
顺铂对女性生殖器官的影响临床似于卵巢早衰,主要表现为(1)小鼠子宫和卵巢分泌功能下降,雌、孕激素水平紊乱,异于正常值。小鼠的卵巢和子宫质量及系数值有所下降；(2)HE染色可以观察到损伤后小鼠卵巢组织闭锁卵泡增多。免疫组化可以看到芳香化酶的表达减少。
补骨脂颗粒大、中、小剂量组不同幅度的调节小鼠的激素水平与回归于正常值,并提高卵巢和子宫质量及系数。且增加发育中的卵泡数量,提高芳香化酶的表达,从而促进底物转化为雌激素。
2细胞水平的研究
2.1药理血清作用不同时间对卵巢颗粒细胞形态的影响
顺铂损伤后,细胞形态发生改变：细胞破碎,贴壁不好,细胞内凹,核周出现空泡,胞质内的细胞器基本消失。补骨脂药理血清组的颗粒细胞相对规则,细胞碎屑较少。
2.2药理血清作用不同时间对卵巢颗粒细胞数量的影响
顺铂损伤前用CCK-8活细胞计数法测出的吸光度值,和顺铂作用后用MTT计数法测出的吸光度值进行比较。顺铂作用前,从吸光度值反映的卵巢颗粒细胞的数量可以作为基数。与顺铂作用后,间接反映的细胞数量对比,可以反映出补骨脂药理血清体外对卵巢颗粒细胞的保护作用,这个主要反映在细胞数量较模型组多。
2.3药理血清作用不同时间对雌激素分泌的影响
颗粒细胞芳香化酶的活性底,且底物含量较低,加入卵泡雌激素(FSH)刺激后,快速提高芳香化酶的活性,从而促进底物大量转化成雌激素,然后随着时间的迁移雌激素分泌量逐渐下降。补骨脂药理血清可以缓慢长久的提高芳香化酶的活性,使雌激素分泌量在一定时间内近于稳,维持在一定的范围内。
综上所述,补骨脂颗粒可以在一定的剂量下对顺铂所致的卵巢损伤表现出良好的保护作用,可以在今后的临床用药方面提供理论指导。
Chemotherapy as the main anti-cancer treatment, which can cause serious damage to the female ovarian structure and function, and lead to premature ovarian failure and related infertility. Therefore, how to treat the tumors while preserving women's ovarian function is a huge medical need, as well as is an important topic worthy of study. Western medicine generally used estrogen replacement therapy (hormone replacement therapy, HRT), but increased risk of estrogen-dependent cancer. Phytoestrogens are a bi-directional regulatory role, avoiding the high side of the HRT and are are the more secure ingredients of treatment. Based on traditional Chinese medicine theory, our laboratory has screened a variety of Zishen Yijing to reconcile qi and blood Chinese medicine, Found that these Chinese medicines have been the role of plant estrogen-like. Psoralen is one of them.
In recent years, the researches on psoralea alleviating the side effects after chemotherapy were increasingly more, mainly for some renal toxicity, immune function degradation, etc. Little research has been conducted in applying Psoralen to protect cisplatin induced ovarian dysfunction. Based on theoretical explanation and experimental activities on applying phytoestrogen to treat gynaecopathia in our laboratory, Psoralen Particles was selected to act on ovary cisplatin- induced. This study may observed whether Psoralen Particles had the protection, and provide theoretical guidance and guidance for clinical use of drugs in the future.
The topic for a two-class research of protective effects of Psoralen on cisplatin induced ovarian dysfunction:
1 The overall level of research
Cisplatin is a cytotoxic non-specific drug, with strong broad-spectrum anti-cancer effects. At the same time it has a strong liver and kidney toxicity. Protective effect of psoralen is reflected in its Entirety.
1.1 The change of morphology and body weight in cisplatin injury mice with gavaging different doses of psoralen Particles
Intraperitoneal injection of cisplatin in mice, then the mice showed dull colour coat and erected-hair, dead-eyes, lying curled, decline in food and weight loss. Stop injection of cisplatin, weight has gone up, but clear differences between the symptoms improved in each group. Particles of different doses of psoralen gavage the mice, they have a good recovery of morphology and body weight in varying degrees.
1.2 The change of Liver, spleen, kidney, device quality in cisplatin injury mice with gavaging different doses of psoralen Particles
There were many studies on cisplatin on liver and kidney toxicity. Intraperitoneal injection of cisplatin result in liver, kidney, spleen injury, such as the decline in the quality, organ coefficient reduced and so on. After psoralen particles gavage, the mice of the organ coefficient values are higher than the model group, especially kidney coefficient. This also shows that the psoralen in the role of nourishing and protecting kidney.
1.3 The change of the quality and morphology of ovarian and uterine in cisplatin injury mice with gavaging different doses of psoralen Particles
The clinical impact of Cisplatin on female genital mutilation is like in premature ovarian failure, mainly for the:(1) Secretion function of mouse uterus and ovaries have gone down. Mice ovary and uterus quality and coefficient decreased. (2) HE staining can be observed in mice ovarian tissue after injury an increase in atretic follicles. HE staining can be observed in mice ovarian tissue after injury an increase in atretic follicles. Immunohistochemistry can be seen the expression of aromatase decrease.
Psoralen large, medium and small-dose group mice with different ranges of regulating hormone levels return to normal, and to improve the quality and coefficient of ovary and uterus. And the increase in the number of developing follicles to enhance the expression of aromatase, thereby contributing to the substrate converted to estrogen.
2 The cell level of research
2.1 Effects on the morphology of ovarian granulosa cells of pharmacological serum at different time
After the effects of cis-platinum, cell morphology changed:cell disruption, poor adhesion, cell concave, perinuclear vacuoles appearance, and Organelles within the cytoplasm disappearance. Granulosa cells of psoralen pharmacological serogroups were relatively regular, and cell debris was less.
2.2 Effects on the amount of ovarian granulosa cells of pharmacological serum at different time
Comparison of the measured absorbance value with CCK-8 cell counting method before Cis-platinum damage, and the measured absorbance value with MTT cell counting method after Cis-platinum damage. Cisplatin before, from the absorbance values reflect the number of ovarian granulosa cells can be used as the base. Cis-platinum after, the value changes that have occurred indirectly reflected the protective effect of ovarian granulosa cells of psoralen in serum pharmacology. This conclusion is mainly manifested in the the number of cells of psoralen group more than the model group.
2.3 Effects on the estrogen secretion of pharmacological serum at different time
Granulosa cell aromatase activity is low, and the lower substrate concentration. After adding estrogen follicles (FSH) stimulation, aromatase activity was rapidly increased, then Catalytic substrate into a large number of estrogens. Over time, the amount of estrogen secretion gradually decreased. Psoralen pharmacological serum can slowly and long-term increase aromatase activity, so that the amount of estrogen at a certain range within a certain period of time maintained.
To sum up, psoralen particles at a certain dose showed good protective effect, on cisplatin-induced ovarian damage. This conclusion may provide theoretical guidance for clinical use of drugs in the future.
此外,近年来补骨脂对于缓解化疗后副作用的研究也日渐趋多,主要是针对一些肾毒性,免疫功能退化等连锁效应。对于使用补骨脂颗粒对损伤的小鼠卵巢进行保护的实验研究很少。结合本实验室关于植物雌激素在妇科疾病的应用理论和研究经验,选用补骨脂颗粒对小鼠顺铂损伤的卵巢进行干预,观察其是否具有保护作用,并对临床用药提供新的依据和指导。
本课题针对补骨脂颗粒对顺铂损伤的卵巢的保护机制进行两个水平的研究：
1整体水平的研究
顺铂是具有细胞毒作用的非特异性药物,具有较强的广谱抗癌作用。同时具有强烈的肝肾毒性作用。补骨脂对其保护作用体现在整体方面。
1.1补骨脂颗粒不同剂量灌胃对顺铂损伤后小鼠形态和体重的影响
顺铂腹腔注射后的小鼠毛色灰暗且炸立,目光呆滞,蜷卧少动,饮食量下降,体重急剧减少。停止注射顺铂,体重都有所回升,但症状改善差别明显。补骨脂颗粒不同剂量灌胃后,小鼠的形态和体重恢复良好,程度不一。
1.2补骨脂颗粒不同剂量灌胃对小鼠肝、脾、肾脏器质量的影响
顺铂对肝、肾毒性作用研究较多,腹腔注射顺铂造成肝、肾、脾脏器的损伤,如质量下降,脏器系数降低的等。用药补骨脂颗粒后,小鼠各项脏器系数的值都较模型组高,尤其是肾脏系数值。这也表明了补骨脂的补肾护肾的作用。
1.3补骨脂颗粒不同剂量灌胃对小鼠卵巢和子宫质量和形态的影响
顺铂对女性生殖器官的影响临床似于卵巢早衰,主要表现为(1)小鼠子宫和卵巢分泌功能下降,雌、孕激素水平紊乱,异于正常值。小鼠的卵巢和子宫质量及系数值有所下降；(2)HE染色可以观察到损伤后小鼠卵巢组织闭锁卵泡增多。免疫组化可以看到芳香化酶的表达减少。
补骨脂颗粒大、中、小剂量组不同幅度的调节小鼠的激素水平与回归于正常值,并提高卵巢和子宫质量及系数。且增加发育中的卵泡数量,提高芳香化酶的表达,从而促进底物转化为雌激素。
2细胞水平的研究
2.1药理血清作用不同时间对卵巢颗粒细胞形态的影响
顺铂损伤后,细胞形态发生改变：细胞破碎,贴壁不好,细胞内凹,核周出现空泡,胞质内的细胞器基本消失。补骨脂药理血清组的颗粒细胞相对规则,细胞碎屑较少。
2.2药理血清作用不同时间对卵巢颗粒细胞数量的影响
顺铂损伤前用CCK-8活细胞计数法测出的吸光度值,和顺铂作用后用MTT计数法测出的吸光度值进行比较。顺铂作用前,从吸光度值反映的卵巢颗粒细胞的数量可以作为基数。与顺铂作用后,间接反映的细胞数量对比,可以反映出补骨脂药理血清体外对卵巢颗粒细胞的保护作用,这个主要反映在细胞数量较模型组多。
2.3药理血清作用不同时间对雌激素分泌的影响
颗粒细胞芳香化酶的活性底,且底物含量较低,加入卵泡雌激素(FSH)刺激后,快速提高芳香化酶的活性,从而促进底物大量转化成雌激素,然后随着时间的迁移雌激素分泌量逐渐下降。补骨脂药理血清可以缓慢长久的提高芳香化酶的活性,使雌激素分泌量在一定时间内近于稳,维持在一定的范围内。
综上所述,补骨脂颗粒可以在一定的剂量下对顺铂所致的卵巢损伤表现出良好的保护作用,可以在今后的临床用药方面提供理论指导。
Chemotherapy as the main anti-cancer treatment, which can cause serious damage to the female ovarian structure and function, and lead to premature ovarian failure and related infertility. Therefore, how to treat the tumors while preserving women's ovarian function is a huge medical need, as well as is an important topic worthy of study. Western medicine generally used estrogen replacement therapy (hormone replacement therapy, HRT), but increased risk of estrogen-dependent cancer. Phytoestrogens are a bi-directional regulatory role, avoiding the high side of the HRT and are are the more secure ingredients of treatment. Based on traditional Chinese medicine theory, our laboratory has screened a variety of Zishen Yijing to reconcile qi and blood Chinese medicine, Found that these Chinese medicines have been the role of plant estrogen-like. Psoralen is one of them.
In recent years, the researches on psoralea alleviating the side effects after chemotherapy were increasingly more, mainly for some renal toxicity, immune function degradation, etc. Little research has been conducted in applying Psoralen to protect cisplatin induced ovarian dysfunction. Based on theoretical explanation and experimental activities on applying phytoestrogen to treat gynaecopathia in our laboratory, Psoralen Particles was selected to act on ovary cisplatin- induced. This study may observed whether Psoralen Particles had the protection, and provide theoretical guidance and guidance for clinical use of drugs in the future.
The topic for a two-class research of protective effects of Psoralen on cisplatin induced ovarian dysfunction:
1 The overall level of research
Cisplatin is a cytotoxic non-specific drug, with strong broad-spectrum anti-cancer effects. At the same time it has a strong liver and kidney toxicity. Protective effect of psoralen is reflected in its Entirety.
1.1 The change of morphology and body weight in cisplatin injury mice with gavaging different doses of psoralen Particles
Intraperitoneal injection of cisplatin in mice, then the mice showed dull colour coat and erected-hair, dead-eyes, lying curled, decline in food and weight loss. Stop injection of cisplatin, weight has gone up, but clear differences between the symptoms improved in each group. Particles of different doses of psoralen gavage the mice, they have a good recovery of morphology and body weight in varying degrees.
1.2 The change of Liver, spleen, kidney, device quality in cisplatin injury mice with gavaging different doses of psoralen Particles
There were many studies on cisplatin on liver and kidney toxicity. Intraperitoneal injection of cisplatin result in liver, kidney, spleen injury, such as the decline in the quality, organ coefficient reduced and so on. After psoralen particles gavage, the mice of the organ coefficient values are higher than the model group, especially kidney coefficient. This also shows that the psoralen in the role of nourishing and protecting kidney.
1.3 The change of the quality and morphology of ovarian and uterine in cisplatin injury mice with gavaging different doses of psoralen Particles
The clinical impact of Cisplatin on female genital mutilation is like in premature ovarian failure, mainly for the:(1) Secretion function of mouse uterus and ovaries have gone down. Mice ovary and uterus quality and coefficient decreased. (2) HE staining can be observed in mice ovarian tissue after injury an increase in atretic follicles. HE staining can be observed in mice ovarian tissue after injury an increase in atretic follicles. Immunohistochemistry can be seen the expression of aromatase decrease.
Psoralen large, medium and small-dose group mice with different ranges of regulating hormone levels return to normal, and to improve the quality and coefficient of ovary and uterus. And the increase in the number of developing follicles to enhance the expression of aromatase, thereby contributing to the substrate converted to estrogen.
2 The cell level of research
2.1 Effects on the morphology of ovarian granulosa cells of pharmacological serum at different time
After the effects of cis-platinum, cell morphology changed:cell disruption, poor adhesion, cell concave, perinuclear vacuoles appearance, and Organelles within the cytoplasm disappearance. Granulosa cells of psoralen pharmacological serogroups were relatively regular, and cell debris was less.
2.2 Effects on the amount of ovarian granulosa cells of pharmacological serum at different time
Comparison of the measured absorbance value with CCK-8 cell counting method before Cis-platinum damage, and the measured absorbance value with MTT cell counting method after Cis-platinum damage. Cisplatin before, from the absorbance values reflect the number of ovarian granulosa cells can be used as the base. Cis-platinum after, the value changes that have occurred indirectly reflected the protective effect of ovarian granulosa cells of psoralen in serum pharmacology. This conclusion is mainly manifested in the the number of cells of psoralen group more than the model group.
2.3 Effects on the estrogen secretion of pharmacological serum at different time
Granulosa cell aromatase activity is low, and the lower substrate concentration. After adding estrogen follicles (FSH) stimulation, aromatase activity was rapidly increased, then Catalytic substrate into a large number of estrogens. Over time, the amount of estrogen secretion gradually decreased. Psoralen pharmacological serum can slowly and long-term increase aromatase activity, so that the amount of estrogen at a certain range within a certain period of time maintained.
To sum up, psoralen particles at a certain dose showed good protective effect, on cisplatin-induced ovarian damage. This conclusion may provide theoretical guidance for clinical use of drugs in the future.
引文
[1]张雯.植物雌激素样活性中药[J].中国现代实用医学杂志,2005,4(7)：50.
[2]国家药典委员会.中华人民共和国药典(一部)[S].北京：化学工业出版社,2005：129-130.
[3]吕娟,斑瑞山,等.补骨脂的化学成分及药理作用研究进展[J].沈阳药科大学学报,1996,13(3)：220-223.
[4]Yangchao Chen, Yuen-Ting Cheung, Long-dong Kong,et al. Transcription regulation of corticotrophin releasing factor gene by furocoumarins isolate from seeds of Psoralea corylifolia[J], Life Science,2008,82:117-1121.
[5]姚三桃,杨滨,徐植灵.补骨脂中补骨脂酚的含量测定[J].中国中药杂志,1995,20(11)：681-683.
[6]徐建国.补骨脂对酪氨酸酶激活作用[J].中药,1991,22(4)：168-169.
[7]刘娟,朱兆荣,等.补骨脂粗黄酮对去卵巢小鼠的影响[J].中兽医学杂志,2005,1：4-6.
[8]Bandarenko A.S,et al, Antimicrobial and Antiviral Activity of Essential oil from Psoralea Drupaeca and its Activit[J].Rasit Resur,1974,10(4):583-588.
[9]Kaul R.N.Kinetics of the Antistaphylococcal Antivity of Bakuchiolon-vitro[J]. Arzneim-Forsch,1976,26(4):486-489.
[10]曹金一,刘京晶,黄文华,等.补骨脂药理作用与临床应用研究进展[J],中药药理与临床,2008,24(6)：89-92.
[11]赵丕文,王大伟,王玲巧,等.用小鼠子宫增重法筛选淫羊藿等10味中药雌激素样作用的实验研究[J].北京中医药大学学报,2006,30(10)：686.
[12]李宜放,刘丽坤,王星,等.升白颗粒治疗化疗所致白细胞减少症的临床观察[J].中药新药与临床药理,2009,20(1)：75-78.
[13]董海涛,刘浩,关念波,等.健脾益肾颗粒减轻528例肿瘤患者化疗毒副作用的临床观察[J].中国中医药信息杂志,2008,5(9)：12-13.
[14]张玲,邓晓玲,江洪,等.健脾益肾颗粒治疗恶性肿瘤化疗副反应观察[J].实用中医药杂志,2006,22(4)：234—235.
[15]陈新军.健脾益肾治疗化疗后血小板减少疗效观察[J].现代中西医结合杂志,2007,16(9)：1191—1192.
[16]USUIT. Pharmaceutical prospects of phytoextrogens[J]. Endocr J,2006,53(1):7.
[17]赵丕文,牛建昭,王继峰,等.补骨脂素的植物雌激素作用及其机制探讨[J].中国中药杂志,2008,33(1)：59-63.
[18]寿清耀,杨荣平,王宾豪,等.补骨脂雌激素样作用的有效成分研究[J].药与临床药 理,2007,18(6)：425-427.
[19]田映碧,罗德纯.中药药理与应用(第二版)[M].北京：人民卫生出版社,2000.
[20]张玉顺,刘玉琦,吴子伦,等.补骨脂酚对小鼠肾脏毒害作用的研究[J]..中药通报,1981,6(3)：30-32.
[21]Clark SM,Wilkinson SMC.Phototoxic contact dermatitis from 5-methoxyp psoralen in aromatherapy oil[J]. Ontact Dermatitis,1998,38(5):289-290.
[22]梅学仁.8-甲氧基补骨脂素在动物体内的代谢研究[J].中草药,1980,11(1)：29.
[23]黄熙.中草药香豆精光敏剂药代动力学一药效学[J].国外研究概况,国外医学·中医中药分册,1990,12(2)：1-5.
[24]蔡宇,曹克俭,殷忠东,等.补骨脂素胶囊对急性白血病多药耐药逆转作用的临床观察[J].中国中医药科技,2002；9(1)：53-54.
[25]曹春林.中药制剂汇编[M].北京：人民卫生出版社,1983,1361-2051.
[26]罗艺晨,刘娟,朱兆荣,等.中药补骨脂的研究进展[J].中兽医学杂志,2007,5：49-53.
[27]黄剑,赵陆华,邹巧根,等.补骨脂化学成分及药理研究进展[J].药学进展,2000,24(4)：212-214.
[1]苏进,高莹.芳香化酶P450在宫颈癌中的研究进展综述[J].陕西医学杂志,2008,37(3)：349-350
[2]Mahendroo M.S., Mendelson C.R., Simpson E.R.. Tissue specific andHormonally controlled alternative promoters regulate aromatase cytochrome P450 gene expression in human adipose tissue[J]. Biol Chem,1993,268:19463-19470.
[3]Chen S, Besman M.J. Sparkes RS, et al. Human aromastase:cDNA cloning, southern blot analysis, and assignment of the gene to chromosome 15[J]. DNA Mol Biol.1988,7:27-38.
[4]Iwabuchi J, Wako S, Tanaka T, et al. Analysis of the P450 aromatase geneexpression in the Xenopus brain and gonad[J]. J. Steroid Biochem MolBiol,2007,107(3-5):149-155.
[5]Gurates B, Sebastian S, Yang S, et al. WT1 and DAX-1 inhibit aromatase P450 expression in human endometrial and endometriotic stromal cells[J].J. Clin Endocrinol Metab,2002,87(9):4369-4377.
[6]Simpson ER, Clyne C, Rubin G, et al. Aromatase-abrief overview[J]. Annu Rev Physiol, 2002,64:93-127.
[7]Graddy IH, Kowalski AA, Sti mmen FA, et al. Multiple isoforms of porcinearomatase are encoded by three distinct genes [J]. J Steroid Biochem Mol Biol,2000,73(1-2):49-57.
[8]Bulun SE, Zeitoun K, Sasano H, et al. Aromatase in aging women [J]. Semin Rcprod Endocrinol,1999,17(4):349-358.
[9]Calzada Mendoza CC, Sanchez EC, Campos RR, et al. Differential romatase(CYP19)expression in human arteries from normal and neoplasicuterus:an immunohistochemical and in situ hybridization study [J]. Front Biosci,2006,11(1):389-393.
[10]Okubo T, Mok SC, Chen S. Regulation of aromatase expression in human Ovarian surface epithelial cells[J]. J Clin Endocrinol Metab,2000,85(12):4889-4899.
[11]张慧锋,王月鹏,李妍.细胞色素P45的研究进展[J].吉林医药学院报,2005,26(3)：55-58.
[12]Dorrington TH.Estradiol-17β biosynthesis in cultured granulose cells From Hypophsectomized immature rats; stimulation by follicle-stimulation hormone[J]. Endocrinology,1975,97:1328-1342.
[13]杨卫东.芳香化酶抑制剂在乳腺癌内分泌治疗中的应用[J].中华现代临床医学杂志,2004,2(11)：46-48
[14]Gurates B, Sebast ian S, Yang S, et al. W T1 and DAX-1 inhibit atomatase P450 expression in human endometrial and endometreotic stromal cells[J]. J Clin Endocrinol Metab,2002,87(9):4369-4377.
[15]Yang SJ, Fang ZJ, Suzuki T, et al. Regulat ion of aromarase P450 expression in endome- treotic and endometrial stromal cells by CCAA Toenhancer binding proteins (Co EBPs):Decreased Co EBP beta in endometriosis in associated with over expression of aromatase[J]. J Clin Endocrinol Metab,2002,87(5):2336-2345.
[16]Bulun SE, Imir G, Utsunomiya H, et al. Aromatase in endometriosis and uterine leiomyomata[J]. J Steroid Biochem Mol Biol,2005,95(1-5):57-62.
[17]Zhao Y, AgarwalVR, Mendelson CR, et al. Estrogen biosynthesis proximal toa breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene [J]. Endocrinology,1996,137(12):5739-5742.
[18]Watanabe M, Noda M, Nakajin S. Effect of epidermal growth factor and prostaglandin on the expression of aromatase (CYP19) in human adrenocorticalcarcinoma cell line NCI-H295R cells [J]. JEndocrinol,2006,188(1):59-68.
[19]Kitawaki J, Kado N, Ish ihara H, et al. Endomet riosis:the pathophysiology as an estrogen-dependent disease[J]. J Steroid Biochem Mole Biol,2003,83:149-155.
[20]李文金,赵春英.芳香化酶与乳腺癌的相关国际研究[J].外科学杂志,2007,1：55-58.
[21]Brodie A, Long B, Lu Q. Aromatase expression in the human breast[J].Breast Cancer Res Treat,1998,49:85-91.
[22]Tekmal RR, Ramachandra N, Gbba S, et al. Over expression of int-5/aromatase in mammary glands of transgenic results in the induction of hyperplasia and nuclear abnormalities[J]. Cancer Res,1996,56(14):3180-3185.
[23]Franks S, Roberts R, Hardy K. Gonadotrophin regimens and oocyte quality in women with polycystic ovaries[J]. Reprod Biomed Online,2003,6(2):181-184.
[25]Zeitoun K, Takayama K, MichaelMD, et al. Stimuiation of aromatase P450promoter(Ⅱ)activity in endometriosis and its inhabition in endometrium are regulated by competitive binding of ST-1 and COUP-TF to the same cis-acting element[J]. Mol Endocrinol,1999,13(2):239-253.
[26]Noble LS, Takayama K, Zeitoun KM,et al. Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells[J]. Clin Endocrinol Metab,1997, 82(5):600-6067.
[27]高维萍,沈阳,张学奎等.子宫腺肌病与盆腔子宫内膜异位症患者性激素受体研究[J].中国现代医学杂志,2003,13(16)：66-67.
[28]Salazar EL, Sojo-Aranda I, Lopez R, et al. The evidence for an Etiological relationship between oral contraceptive use and dysplastic change in cervical tissue[J]. J Gynecol Endocrinol,2001,15:23-28.
[29]Deligeo roglou E, M ichailidis E, Creatsas G. Oral contraceptives and reproductive system cancer[J]. J Ann NY Acad Sci,2003,997:199-208.
[30]Hareesh B, Nair NK, Ya GL, et al. Induct ion of aromatase expression in cervical carcinomas:Effects of endogenous estrogen on cervical cancer cell proliferation[J]. J Cancer Res,2005,65:(23)11164-11173.
[32]徐行丽,贾庆兰,崔秀娟,等.子宫肌瘤组织中性激素含量和P450arom的表达及其与发病的关系[J].第二军医大学学报,2005,26(5)：585-586.
[33]Hiroshi S, Makio S, Tomoya S, et al. In situ estrogen synthesized by aromatase P450 in uterine leiomyoma cells promotes cell growth probably via an autocrine/intracrine mechanism[J]. Endocrinology,2000,141(10):3852-3861.
[34]Makio S, Hiroshi S, Tomoya S, et al. Inhibition of in situ expression of aromatase P450 in leiomyoma of the uterus by leuprorelin acetate[J]. Journal of Clinical Endocrinology and Metabolism,2001,86(11):5405-5411.
[35]MorD, Yue W, Santen R, et al. Macrophages, Estrogen and the microenvironment of breast[J]. J Cancer,1998,67:403-411.
[1]韩锐主编.肿瘤化学预防与治疗[M].北京医科大学中国协和医科大学联合出版社.1991年：283.
[2]Robson H, Meyer S, Shalet SM, et al. Platinum agents in the treatment of osteosarcoma: efficacy of cisplatin vs. carboplatin in human osteosarcoma cell lines[J]. Med Pediatr Oncol, 2002,39 (6):573-580.
[3]Sato S, Yamate J, SaitoT, et al. Protective effect of taurine against renal interstitial fibrosis of rats induced by cisplatin[J]. Naunyn Schmiedebergs Arch Pharmacol,2002, 365(4):277-283.
[4]Leonetti C, Biroccio A, Gabellini C, et al. Alpha-tocophe protects against cisplatin-induced toxicity without interfering wantitumor efficacy[J].Int J Cancer,2003,104(2):243-250.
[5]齐聪.顺铂腹腔内给药对大鼠卵巢的毒性作用[J].上海医科大学学报,2000,27(4)：324-325.
[6]艾浩,牛建昭,薛晓鸥,等.顺铂致小鼠卵巢功能早衰肝肾阴虚证机制研究[J].北京中医药大学学报,2006,6(29)：401—403.
[7]Yang BH, Parkin DM, Cai L, et al.Cancer burden and trends in the Asian Pacific Rim region[J]. Asian Pac J Cancer Prev,2004,5(2):96-111
[8]FoxH. The pathology of premature ovarian failure[J]. J Pathol,1992,167(4):357-363.
[9]ZHANG W. Phytoestrogenic effect of Chinese medicine[J].China J Current PracticalMed[中国现代实用医学杂志),2005,4(7)：50-51.
[10]赵丕文,牛建昭,王继峰,等.6种中药活性成分植物雌激素作用的比较研究[J].中国药学杂,2007,42(24)：1852-1855.
[11]牛建昭,赵丕文,王继峰,等.补骨脂等5种中药植物雌激素活性的实验研究[J].北京中医药大学学报,2008,31(10)：676-681.
[121赵丕文,王大伟,牛建昭,等.红花等10种中药的植物雌激素活性研究[J].中国中药杂志,2007,32(5)：436-439.
[13]沈铿.卵巢恶性肿瘤的化疗[J].中国临床医生,1999,27(2)：20-21.
[14]杨国宏,张际绯.卵巢癌化疗的研究进展.牡丹江医学院学报[J],2006,27(2)：57-61.
[15]杨平,初照成,王实,等.顺铂对人卵巢癌CAOV_3细胞端粒酶活性和凋亡的影响[J].中国全科医学,2005,8(11)：896-897.
[16]Blakley BW, CohenJI, Doolittle ND, et al. Strategies for prevention of toxicity caused by platinum-based chemotherapy [J]. Laryngoscope,2002,112:1997-2001.
[17]Mansour MA, Mostafa AM, Nagi MN, et al. Protective effect of aminoguanidine against nephrotoxicity induced by cisplatin in normal rats [J]. Comp Biochem Physiol CToxicol Pharmacol,2002,132:123-12
[18]孔繁斗,吕申,吴琳.顺铂对雌性大鼠骨密度影响的实验研究[J].中国骨质疏松杂志,2005(12)：175-177.
[19]邓成艳,黄荣丽,连利娟,等.顺铂的毒副作用及其防治[J].中华妇产科杂志,1995,30(6)：376-379.
[20]刘丽娟,苏乐群.顺铂的毒性及其防治[J].山东医药,1996,36(7)：51.
[21]梁月琴.顺铂肾毒性的防治措施[J].河北医药,1995,17(4)：238-239.
[22]李革新,金亚平,陆春伟,等.顺铂肝毒性的实验研究[J].中国工业医学杂志,2005,1 8(6)：352-353.
[23]齐聪.顺铂腹腔内给药对大鼠卵巢的毒性作用[J].上海医科大学学报,2000,27(4)：324-325.
[24]艾浩,牛建昭,薛晓鸥,等.顺铂致小鼠卵巢功能早衰肝肾阴虚证机制研究[J].北京中医药大学学报,2006,6(29)：401-403.
[25]蔡宇,曹克俭,殷忠东.补骨脂素逆转急性白血病多药耐药的临床观察[J].中国中医药科技,2002；(1)：26.
[26]蔡宇.补骨脂胶囊对24例白血病化疗后免疫功能的影响[J].陕西中医,2003,24(12)：1059-1060.
[27]牛建昭,薛晓鸥主编.中西医结合女性生殖内分泌学[M].北京.人民军医出版社,2008年6月：30-31.
[28]艾浩,牛建昭,薛晓鸥,等.顺铂腹腔注射对小鼠卵巢和子宫形态的影响[J].第四军医大学学报,2008,29(9)：30.
[29]艾浩,牛建昭,薛晓鸥,等.化疗损伤性卵巢功能早衰小鼠动物模型的研究[J].中国实验动物学报,2007(1)：12-15.
[30]艾浩,牛建昭,薛晓鸥,等.顺铂腹腔注射对小鼠卵巢相关基因表达谱的影响[J].医学 研究生学报,2007,20(3)：23-28.
[31]汪晖主编.药理学实验[M].湖北.湖北科学技术出版社,2005年9月：22.
[32]靳玉甫.卵巢颗粒细胞P450芳香化酶研究进展[J].广西医科大学学,2008,25(6)：972-974.
[33]Simpson ER, Clyne C, Rubin G, et al.Aromatase-abrief overview[J]. Annu Rev Physiol, 2002,64:93-127.
[34]Hunter MH, Sterrett JJ. Polycystic ovary syndrome:it's not just infertility[J]. Am Fam Physician,2000,62(5):1079-1088,1090.
[35]Richards JS, Russell DL, Ochsner S, et al. Ovulation:new dimensions and new regulators of the inflammatory-like response[J]. Annu Rev Physiol,2002,64:69-92.
[36]Sommersberg B,Bulling A,Salzer U,et al.Gap junction communication and connexin 43 gene expression in a rat granulosa cell line:regulation by follicle-stimulating hormone[J]. Biol Reprod,2000,63(6):1661-1668.
[37]Gurates B, Sebastian S, Yang S, et al. WT1 and DAX1 inhibit aromatase P450 expression in human endometrial and endometriotic stromal cells[J]. J Clin Endocrinol Metab, 2002,87(9):4369-4377.
[38]Horowitz NS, HuaJ, GibbRK, et al. The role of topotecan for extending the platinum-free interval in recurrent ovarian cancer:an in vitro model[J]. Gynecol Oncol,2004,94:67-73.
[39]薛晓鸥,杨毅,艾浩,等.顺铂对正常大鼠卵巢颗粒细胞的毒性和金雀黄素的保护作用[J].中国妇产科临床杂志,2007,8(1)：38-40.
[40]Bendell JJ, Dorrington J. Estradiol-17 beta stimulatinf hormone receptor expression in the rat ovary:increases during prepubertal development and regulation by the opposing actions of transforming growth factors beta and alpha[J]. Biol Reprod,1994,50:940-948.
[41]Klinghoffer RA, Mueting-Nelsen PF, Faerman A, et al. The two PDGF receptors maintain conserved signaling in vivo despite divergent embryological functions[J]. Mol Cell, 2001,7 (2):343-354.
[2]国家药典委员会.中华人民共和国药典(一部)[S].北京：化学工业出版社,2005：129-130.
[3]吕娟,斑瑞山,等.补骨脂的化学成分及药理作用研究进展[J].沈阳药科大学学报,1996,13(3)：220-223.
[4]Yangchao Chen, Yuen-Ting Cheung, Long-dong Kong,et al. Transcription regulation of corticotrophin releasing factor gene by furocoumarins isolate from seeds of Psoralea corylifolia[J], Life Science,2008,82:117-1121.
[5]姚三桃,杨滨,徐植灵.补骨脂中补骨脂酚的含量测定[J].中国中药杂志,1995,20(11)：681-683.
[6]徐建国.补骨脂对酪氨酸酶激活作用[J].中药,1991,22(4)：168-169.
[7]刘娟,朱兆荣,等.补骨脂粗黄酮对去卵巢小鼠的影响[J].中兽医学杂志,2005,1：4-6.
[8]Bandarenko A.S,et al, Antimicrobial and Antiviral Activity of Essential oil from Psoralea Drupaeca and its Activit[J].Rasit Resur,1974,10(4):583-588.
[9]Kaul R.N.Kinetics of the Antistaphylococcal Antivity of Bakuchiolon-vitro[J]. Arzneim-Forsch,1976,26(4):486-489.
[10]曹金一,刘京晶,黄文华,等.补骨脂药理作用与临床应用研究进展[J],中药药理与临床,2008,24(6)：89-92.
[11]赵丕文,王大伟,王玲巧,等.用小鼠子宫增重法筛选淫羊藿等10味中药雌激素样作用的实验研究[J].北京中医药大学学报,2006,30(10)：686.
[12]李宜放,刘丽坤,王星,等.升白颗粒治疗化疗所致白细胞减少症的临床观察[J].中药新药与临床药理,2009,20(1)：75-78.
[13]董海涛,刘浩,关念波,等.健脾益肾颗粒减轻528例肿瘤患者化疗毒副作用的临床观察[J].中国中医药信息杂志,2008,5(9)：12-13.
[14]张玲,邓晓玲,江洪,等.健脾益肾颗粒治疗恶性肿瘤化疗副反应观察[J].实用中医药杂志,2006,22(4)：234—235.
[15]陈新军.健脾益肾治疗化疗后血小板减少疗效观察[J].现代中西医结合杂志,2007,16(9)：1191—1192.
[16]USUIT. Pharmaceutical prospects of phytoextrogens[J]. Endocr J,2006,53(1):7.
[17]赵丕文,牛建昭,王继峰,等.补骨脂素的植物雌激素作用及其机制探讨[J].中国中药杂志,2008,33(1)：59-63.
[18]寿清耀,杨荣平,王宾豪,等.补骨脂雌激素样作用的有效成分研究[J].药与临床药 理,2007,18(6)：425-427.
[19]田映碧,罗德纯.中药药理与应用(第二版)[M].北京：人民卫生出版社,2000.
[20]张玉顺,刘玉琦,吴子伦,等.补骨脂酚对小鼠肾脏毒害作用的研究[J]..中药通报,1981,6(3)：30-32.
[21]Clark SM,Wilkinson SMC.Phototoxic contact dermatitis from 5-methoxyp psoralen in aromatherapy oil[J]. Ontact Dermatitis,1998,38(5):289-290.
[22]梅学仁.8-甲氧基补骨脂素在动物体内的代谢研究[J].中草药,1980,11(1)：29.
[23]黄熙.中草药香豆精光敏剂药代动力学一药效学[J].国外研究概况,国外医学·中医中药分册,1990,12(2)：1-5.
[24]蔡宇,曹克俭,殷忠东,等.补骨脂素胶囊对急性白血病多药耐药逆转作用的临床观察[J].中国中医药科技,2002；9(1)：53-54.
[25]曹春林.中药制剂汇编[M].北京：人民卫生出版社,1983,1361-2051.
[26]罗艺晨,刘娟,朱兆荣,等.中药补骨脂的研究进展[J].中兽医学杂志,2007,5：49-53.
[27]黄剑,赵陆华,邹巧根,等.补骨脂化学成分及药理研究进展[J].药学进展,2000,24(4)：212-214.
[1]苏进,高莹.芳香化酶P450在宫颈癌中的研究进展综述[J].陕西医学杂志,2008,37(3)：349-350
[2]Mahendroo M.S., Mendelson C.R., Simpson E.R.. Tissue specific andHormonally controlled alternative promoters regulate aromatase cytochrome P450 gene expression in human adipose tissue[J]. Biol Chem,1993,268:19463-19470.
[3]Chen S, Besman M.J. Sparkes RS, et al. Human aromastase:cDNA cloning, southern blot analysis, and assignment of the gene to chromosome 15[J]. DNA Mol Biol.1988,7:27-38.
[4]Iwabuchi J, Wako S, Tanaka T, et al. Analysis of the P450 aromatase geneexpression in the Xenopus brain and gonad[J]. J. Steroid Biochem MolBiol,2007,107(3-5):149-155.
[5]Gurates B, Sebastian S, Yang S, et al. WT1 and DAX-1 inhibit aromatase P450 expression in human endometrial and endometriotic stromal cells[J].J. Clin Endocrinol Metab,2002,87(9):4369-4377.
[6]Simpson ER, Clyne C, Rubin G, et al. Aromatase-abrief overview[J]. Annu Rev Physiol, 2002,64:93-127.
[7]Graddy IH, Kowalski AA, Sti mmen FA, et al. Multiple isoforms of porcinearomatase are encoded by three distinct genes [J]. J Steroid Biochem Mol Biol,2000,73(1-2):49-57.
[8]Bulun SE, Zeitoun K, Sasano H, et al. Aromatase in aging women [J]. Semin Rcprod Endocrinol,1999,17(4):349-358.
[9]Calzada Mendoza CC, Sanchez EC, Campos RR, et al. Differential romatase(CYP19)expression in human arteries from normal and neoplasicuterus:an immunohistochemical and in situ hybridization study [J]. Front Biosci,2006,11(1):389-393.
[10]Okubo T, Mok SC, Chen S. Regulation of aromatase expression in human Ovarian surface epithelial cells[J]. J Clin Endocrinol Metab,2000,85(12):4889-4899.
[11]张慧锋,王月鹏,李妍.细胞色素P45的研究进展[J].吉林医药学院报,2005,26(3)：55-58.
[12]Dorrington TH.Estradiol-17β biosynthesis in cultured granulose cells From Hypophsectomized immature rats; stimulation by follicle-stimulation hormone[J]. Endocrinology,1975,97:1328-1342.
[13]杨卫东.芳香化酶抑制剂在乳腺癌内分泌治疗中的应用[J].中华现代临床医学杂志,2004,2(11)：46-48
[14]Gurates B, Sebast ian S, Yang S, et al. W T1 and DAX-1 inhibit atomatase P450 expression in human endometrial and endometreotic stromal cells[J]. J Clin Endocrinol Metab,2002,87(9):4369-4377.
[15]Yang SJ, Fang ZJ, Suzuki T, et al. Regulat ion of aromarase P450 expression in endome- treotic and endometrial stromal cells by CCAA Toenhancer binding proteins (Co EBPs):Decreased Co EBP beta in endometriosis in associated with over expression of aromatase[J]. J Clin Endocrinol Metab,2002,87(5):2336-2345.
[16]Bulun SE, Imir G, Utsunomiya H, et al. Aromatase in endometriosis and uterine leiomyomata[J]. J Steroid Biochem Mol Biol,2005,95(1-5):57-62.
[17]Zhao Y, AgarwalVR, Mendelson CR, et al. Estrogen biosynthesis proximal toa breast tumor is stimulated by PGE2 via cyclic AMP, leading to activation of promoter II of the CYP19 (aromatase) gene [J]. Endocrinology,1996,137(12):5739-5742.
[18]Watanabe M, Noda M, Nakajin S. Effect of epidermal growth factor and prostaglandin on the expression of aromatase (CYP19) in human adrenocorticalcarcinoma cell line NCI-H295R cells [J]. JEndocrinol,2006,188(1):59-68.
[19]Kitawaki J, Kado N, Ish ihara H, et al. Endomet riosis:the pathophysiology as an estrogen-dependent disease[J]. J Steroid Biochem Mole Biol,2003,83:149-155.
[20]李文金,赵春英.芳香化酶与乳腺癌的相关国际研究[J].外科学杂志,2007,1：55-58.
[21]Brodie A, Long B, Lu Q. Aromatase expression in the human breast[J].Breast Cancer Res Treat,1998,49:85-91.
[22]Tekmal RR, Ramachandra N, Gbba S, et al. Over expression of int-5/aromatase in mammary glands of transgenic results in the induction of hyperplasia and nuclear abnormalities[J]. Cancer Res,1996,56(14):3180-3185.
[23]Franks S, Roberts R, Hardy K. Gonadotrophin regimens and oocyte quality in women with polycystic ovaries[J]. Reprod Biomed Online,2003,6(2):181-184.
[25]Zeitoun K, Takayama K, MichaelMD, et al. Stimuiation of aromatase P450promoter(Ⅱ)activity in endometriosis and its inhabition in endometrium are regulated by competitive binding of ST-1 and COUP-TF to the same cis-acting element[J]. Mol Endocrinol,1999,13(2):239-253.
[26]Noble LS, Takayama K, Zeitoun KM,et al. Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells[J]. Clin Endocrinol Metab,1997, 82(5):600-6067.
[27]高维萍,沈阳,张学奎等.子宫腺肌病与盆腔子宫内膜异位症患者性激素受体研究[J].中国现代医学杂志,2003,13(16)：66-67.
[28]Salazar EL, Sojo-Aranda I, Lopez R, et al. The evidence for an Etiological relationship between oral contraceptive use and dysplastic change in cervical tissue[J]. J Gynecol Endocrinol,2001,15:23-28.
[29]Deligeo roglou E, M ichailidis E, Creatsas G. Oral contraceptives and reproductive system cancer[J]. J Ann NY Acad Sci,2003,997:199-208.
[30]Hareesh B, Nair NK, Ya GL, et al. Induct ion of aromatase expression in cervical carcinomas:Effects of endogenous estrogen on cervical cancer cell proliferation[J]. J Cancer Res,2005,65:(23)11164-11173.
[32]徐行丽,贾庆兰,崔秀娟,等.子宫肌瘤组织中性激素含量和P450arom的表达及其与发病的关系[J].第二军医大学学报,2005,26(5)：585-586.
[33]Hiroshi S, Makio S, Tomoya S, et al. In situ estrogen synthesized by aromatase P450 in uterine leiomyoma cells promotes cell growth probably via an autocrine/intracrine mechanism[J]. Endocrinology,2000,141(10):3852-3861.
[34]Makio S, Hiroshi S, Tomoya S, et al. Inhibition of in situ expression of aromatase P450 in leiomyoma of the uterus by leuprorelin acetate[J]. Journal of Clinical Endocrinology and Metabolism,2001,86(11):5405-5411.
[35]MorD, Yue W, Santen R, et al. Macrophages, Estrogen and the microenvironment of breast[J]. J Cancer,1998,67:403-411.
[1]韩锐主编.肿瘤化学预防与治疗[M].北京医科大学中国协和医科大学联合出版社.1991年：283.
[2]Robson H, Meyer S, Shalet SM, et al. Platinum agents in the treatment of osteosarcoma: efficacy of cisplatin vs. carboplatin in human osteosarcoma cell lines[J]. Med Pediatr Oncol, 2002,39 (6):573-580.
[3]Sato S, Yamate J, SaitoT, et al. Protective effect of taurine against renal interstitial fibrosis of rats induced by cisplatin[J]. Naunyn Schmiedebergs Arch Pharmacol,2002, 365(4):277-283.
[4]Leonetti C, Biroccio A, Gabellini C, et al. Alpha-tocophe protects against cisplatin-induced toxicity without interfering wantitumor efficacy[J].Int J Cancer,2003,104(2):243-250.
[5]齐聪.顺铂腹腔内给药对大鼠卵巢的毒性作用[J].上海医科大学学报,2000,27(4)：324-325.
[6]艾浩,牛建昭,薛晓鸥,等.顺铂致小鼠卵巢功能早衰肝肾阴虚证机制研究[J].北京中医药大学学报,2006,6(29)：401—403.
[7]Yang BH, Parkin DM, Cai L, et al.Cancer burden and trends in the Asian Pacific Rim region[J]. Asian Pac J Cancer Prev,2004,5(2):96-111
[8]FoxH. The pathology of premature ovarian failure[J]. J Pathol,1992,167(4):357-363.
[9]ZHANG W. Phytoestrogenic effect of Chinese medicine[J].China J Current PracticalMed[中国现代实用医学杂志),2005,4(7)：50-51.
[10]赵丕文,牛建昭,王继峰,等.6种中药活性成分植物雌激素作用的比较研究[J].中国药学杂,2007,42(24)：1852-1855.
[11]牛建昭,赵丕文,王继峰,等.补骨脂等5种中药植物雌激素活性的实验研究[J].北京中医药大学学报,2008,31(10)：676-681.
[121赵丕文,王大伟,牛建昭,等.红花等10种中药的植物雌激素活性研究[J].中国中药杂志,2007,32(5)：436-439.
[13]沈铿.卵巢恶性肿瘤的化疗[J].中国临床医生,1999,27(2)：20-21.
[14]杨国宏,张际绯.卵巢癌化疗的研究进展.牡丹江医学院学报[J],2006,27(2)：57-61.
[15]杨平,初照成,王实,等.顺铂对人卵巢癌CAOV_3细胞端粒酶活性和凋亡的影响[J].中国全科医学,2005,8(11)：896-897.
[16]Blakley BW, CohenJI, Doolittle ND, et al. Strategies for prevention of toxicity caused by platinum-based chemotherapy [J]. Laryngoscope,2002,112:1997-2001.
[17]Mansour MA, Mostafa AM, Nagi MN, et al. Protective effect of aminoguanidine against nephrotoxicity induced by cisplatin in normal rats [J]. Comp Biochem Physiol CToxicol Pharmacol,2002,132:123-12
[18]孔繁斗,吕申,吴琳.顺铂对雌性大鼠骨密度影响的实验研究[J].中国骨质疏松杂志,2005(12)：175-177.
[19]邓成艳,黄荣丽,连利娟,等.顺铂的毒副作用及其防治[J].中华妇产科杂志,1995,30(6)：376-379.
[20]刘丽娟,苏乐群.顺铂的毒性及其防治[J].山东医药,1996,36(7)：51.
[21]梁月琴.顺铂肾毒性的防治措施[J].河北医药,1995,17(4)：238-239.
[22]李革新,金亚平,陆春伟,等.顺铂肝毒性的实验研究[J].中国工业医学杂志,2005,1 8(6)：352-353.
[23]齐聪.顺铂腹腔内给药对大鼠卵巢的毒性作用[J].上海医科大学学报,2000,27(4)：324-325.
[24]艾浩,牛建昭,薛晓鸥,等.顺铂致小鼠卵巢功能早衰肝肾阴虚证机制研究[J].北京中医药大学学报,2006,6(29)：401-403.
[25]蔡宇,曹克俭,殷忠东.补骨脂素逆转急性白血病多药耐药的临床观察[J].中国中医药科技,2002；(1)：26.
[26]蔡宇.补骨脂胶囊对24例白血病化疗后免疫功能的影响[J].陕西中医,2003,24(12)：1059-1060.
[27]牛建昭,薛晓鸥主编.中西医结合女性生殖内分泌学[M].北京.人民军医出版社,2008年6月：30-31.
[28]艾浩,牛建昭,薛晓鸥,等.顺铂腹腔注射对小鼠卵巢和子宫形态的影响[J].第四军医大学学报,2008,29(9)：30.
[29]艾浩,牛建昭,薛晓鸥,等.化疗损伤性卵巢功能早衰小鼠动物模型的研究[J].中国实验动物学报,2007(1)：12-15.
[30]艾浩,牛建昭,薛晓鸥,等.顺铂腹腔注射对小鼠卵巢相关基因表达谱的影响[J].医学 研究生学报,2007,20(3)：23-28.
[31]汪晖主编.药理学实验[M].湖北.湖北科学技术出版社,2005年9月：22.
[32]靳玉甫.卵巢颗粒细胞P450芳香化酶研究进展[J].广西医科大学学,2008,25(6)：972-974.
[33]Simpson ER, Clyne C, Rubin G, et al.Aromatase-abrief overview[J]. Annu Rev Physiol, 2002,64:93-127.
[34]Hunter MH, Sterrett JJ. Polycystic ovary syndrome:it's not just infertility[J]. Am Fam Physician,2000,62(5):1079-1088,1090.
[35]Richards JS, Russell DL, Ochsner S, et al. Ovulation:new dimensions and new regulators of the inflammatory-like response[J]. Annu Rev Physiol,2002,64:69-92.
[36]Sommersberg B,Bulling A,Salzer U,et al.Gap junction communication and connexin 43 gene expression in a rat granulosa cell line:regulation by follicle-stimulating hormone[J]. Biol Reprod,2000,63(6):1661-1668.
[37]Gurates B, Sebastian S, Yang S, et al. WT1 and DAX1 inhibit aromatase P450 expression in human endometrial and endometriotic stromal cells[J]. J Clin Endocrinol Metab, 2002,87(9):4369-4377.
[38]Horowitz NS, HuaJ, GibbRK, et al. The role of topotecan for extending the platinum-free interval in recurrent ovarian cancer:an in vitro model[J]. Gynecol Oncol,2004,94:67-73.
[39]薛晓鸥,杨毅,艾浩,等.顺铂对正常大鼠卵巢颗粒细胞的毒性和金雀黄素的保护作用[J].中国妇产科临床杂志,2007,8(1)：38-40.
[40]Bendell JJ, Dorrington J. Estradiol-17 beta stimulatinf hormone receptor expression in the rat ovary:increases during prepubertal development and regulation by the opposing actions of transforming growth factors beta and alpha[J]. Biol Reprod,1994,50:940-948.
[41]Klinghoffer RA, Mueting-Nelsen PF, Faerman A, et al. The two PDGF receptors maintain conserved signaling in vivo despite divergent embryological functions[J]. Mol Cell, 2001,7 (2):343-354.