益肾填精中药拮抗环境内分泌干扰物引致青春前期大鼠性腺发育不良的作用机制  

Mechanism of Antagonistic Effects of TKRE on Environmental Endocrine Disruptors Inducing Gonadal Dysgenesis in Prepubertal Male Rats

作　　者：高连连[1] 李祥婷[1] 谢长明[2] 蔡德培[1] 

机构地区：[1]复旦大学附属儿科医院,上海201102 [2]复旦大学公共卫生学院,上海200032

出　　处：《中国生物化学与分子生物学报》2014年第8期787-796,共10页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.30371820;No.81373692)~~

摘　　要：邻苯二甲酸二(2-乙基己基)酯(di-2-ethylhexylphthalate,DEHP)及氯氰菊酯(cypermethrin,CYP)是我国广泛存在的两种环境内分泌干扰物(environmental endocrine disruptors,EEDs),具有显著的抗雄激素活性及生殖毒性,可致雄性性腺发育不良.祖国传统医学认为,性腺发育不良属肾精亏虚、肾气不足,临床采用益肾填精中药治疗取得显著疗效,但其具体机制尚不清楚.本实验主要研究益肾填精中药拮抗EEDs——DEHP及CYP引致青春前期大鼠性腺发育不良的作用机制.实验中染毒组分别饲喂500 mg/kg DEHP,80 mg/kg CYP及500 mg/kg DEHP+80 mg/kg CYP,治疗组采用40 mg/kg益肾填精中药与相应染毒物质同时饲喂.研究结果显示,DEHP、CYP单独及联合染毒组的青春前期大鼠睾丸重量、睾丸系数及血清睾酮水平均显著下调;睾丸氧化应激指标MDA含量、GSH-Px活性明显上升;病理组织及超微结构显示睾丸形态萎缩;睾丸支持细胞功能相关的基因与蛋白表达均出现不同程度的下调.益肾填精中药治疗干预后,睾丸重量、睾丸系数及血清睾酮水平均显著增加并接近对照组水平;睾丸形态明显改善,细胞数量增加;睾丸氧化应激水平下降;实时荧光定量PCR及Western印迹显示睾丸支持细胞功能相关的基因与蛋白的表达水平显著上调.本研究证实,益肾填精中药对DEHP及CYP的抗雄激素活性及生殖毒性有显著拮抗作用,可明显拮抗染毒物质诱导的氧化应激作用,促进睾酮分泌,并改善睾丸支持细胞功能,这可能是益肾填精中药有效拮抗EEDs抗雄激素活性及其生殖毒性的主要作用机制之一.Di-（2-ethylhexyl） phthalate （DEHP） and cypermethrin （CYP） are common environmental endocrine disruptors （EEDs） in China, which are known to induce gonadal dysgenesis in pubertal mammals. The traditional Chinese medicine suggests that gonadal dysgenesis is renal essence deficiency, and tonifying kidney drugs are believed to be appropriate and beneficial treatment agents and have been approved to achieve significant clinical efficacy. The present study was designed to investigate the effects of Chinese herb medicine for tonifying kidney to replenish essence （TKRE） on prepubertal male rats ofgonadal dysgenesis induced by DEHP and CYP. The exposure groups were gavaged for 28 days with 500 mg/kg of DEHP, 80 mg/kg of CYP and mixture of DEHP and CYP, respectively. The three corresponding treatment groups were simultaneously supplemented with 40 mg/kg of Chinese herb medicine. Rats exposed to DEHP and CYP showed severe alterations of testicular morphology and sertoli cell function. However, those changes were significantly reversed by simultaneously supplemented Chinese herb medicine. Testes weight, testes coefficient and serum level of testosterone were significantly increased. Histology and ultrastructure of testes revealed a significantly amelioration in the number and morphology of germ ceils and sertoli ceils. Oxidative stress was also significantly decreased. Gene and protein expressions related to sertoli cell function were up-regulated in different stages. Taken together, these results validated the antiandrogenic effects of DEHP and CYP exposure on prepubertal male rats. Our results demonstrated that Chinese herb medicine for tonifying kidney to replenish essence could significantly antagonize the anti-androgenic activity and reproductive toxicity of DEHP and C/yP. The melioration of sertoli cell function might be involved in the efficacy of this herbal mixture.

关 键 词：环境内分泌干扰物 性腺发育不良 益肾填精中药 支持细胞 氧化应激 

分 类 号：R725.8[医药卫生—儿科]