雷公藤多苷对雄性SD大鼠生殖系统损伤的动态变化及其可能机制  

Dynamic changes and mechanism of reproductive system injury induced by Tripterygium glycosides in male SD rats

作　　者：郭健敏 黄远铿 雷夏凌 韩重 梁纯[3] 杨威 GUO Jian-min;HUANG Yuan-keng;LEI Xia-ling;HAN Zhong;LIANG Chun;YANG Wei(Guangdong Key Laboratory of Animal Conservation and Resource Utilization,Guangdong Public Laboratory Wild Animal Conservation and Utilization,Guangdong Institute of Applied Biological Resources,Guangzhou 510990,China;Guangdong Lewwin Pharmaceutical Research Institute Co.,Ltd.,Guangzhou 510990,China;Hongkong University of Science and Technology,Hongkong 999077,China)

机构地区：[1]广东省生物资源应用研究所,广东省动物保护与资源利用重点实验室,广东省野生动物保护与利用公共实验室,广东广州510260 [2]广东莱恩医药研究院有限公司,广东广州510990 [3]香港科技大学,中国香港999077

出　　处：《中国药理学与毒理学杂志》2018年第6期469-476,共8页Chinese Journal of Pharmacology and Toxicology

基　　金：广东省科学院创新药物安全性评价研究团队专项资金资助项目(2016GDASRC-0104); 国家重点基础研究发展计划资助项目(2009CB522800-G)

摘　　要：目的观察雄性SD大鼠青春期至性成熟期用雷公藤多苷(GTW)对生殖系统的损伤过程及其机制。方法 5周龄SD大鼠180只,随机分为正常对照组、GTW 37.8和94.5 mg·kg^(-1)组,连续ig给药90 d,每组分别于给药后第7天(d7),d15,d30,d60,d90和d120(恢复30 d)剖检,生殖脏器称重计算脏器系数;取附睾进行伊红染色观察精子形态,计算未成熟精子率和畸形精子率;HE染色观察生殖脏器组织病理变化。各组d60取血检测促性腺激素释放激素(Gn RH)、黄体生成素(LH)、卵泡刺激素(FSH)和睾酮(T)水平,免疫组化法检测d60,d90和d120下丘脑、垂体、睾丸和附睾中雄激素受体(AR)表达。结果正常对照组大鼠精子形态及发育正常,生殖脏器外观正常且未见病理改变;与正常对照组相比,GTW 37.8和94.5 mg·kg^(-1)组自d7起,未成熟精子率和异常精子率显著增加(P<0.01),睾丸和附睾系数显著降低(P<0.01),组织病理学检查可见睾丸萎缩且生精细胞减少甚至消失,附睾管空虚未见成熟精子,表现严重生精障碍,d120(恢复30 d)时未见明显改善。与正常对照组比较,GTW 37.8和94.5 mg·kg^(-1)组大鼠d60 LH,FSH和T分泌显著降低(P<0.01);GTW 94.5 mg·kg^(-1)组下丘脑d60和d90及睾丸和附睾d60,d90和d120 AR表达显著降低(P<0.01)。结论 GTW对雄性大鼠生殖器官均有明显损伤,其毒性作用于精子发生的整个过程,影响生精功能和精子发育形态,长期给药损伤可加重且长时间无法恢复。其机制可能与抑制LH,FSH和T分泌以及下调下丘脑、睾丸和附睾中AR表达有关。OBJECTIVE To investigate the dynamic process and mechanism reproductive system injury caused by Tripterygium glycosides（GTW） in male SD rats from adolescence to sexual maturation.METHODS One hundred and eighty 5-week-old Sprague-Dawley rats were randomly divided into normal control group,and GTW 37.8 and 94.5 mg·kg^-1 groups.Each group set d7,d15,d30,d60,d90,and d120（recovery for 30 d） terminal time points.At each necropsy time point,reproductive organs were weighed to calculate the organ coefficient,epididymis was taken for spermatozoa examination by eosin staining,and organs were treated with HE staining for pathological examination.Blood was taken at d60 for the detection of reproductive hormones,including gonadotropin-releasing hormone（Gn RH）,luteinizing hormone（LH）,follicle stimulating hormone（FSH）,and testosterone（T）.At d60,d90 and d120,androgen receptor（AR） expressions in tissues of the hypothalamus,pituitary,testis,epididymis and androgen were detected by immunohistochemistry.RESULTS The rats in normal control group had normal sperm morphology and development,the appearance of reproductive organs was normal and no pathological changes were observed.In GTW 37.8 and 94.5 mg·kg^-1 groups,the percentage of immature spermatozoa and abnormal spermatozoa increased,while the testis and epididymis index decreased（P〈0.01） from d7.The histopathological result showed not only testicular atrophy,accompanied by the decrease and disappearance of spermatogenic cells,but also an empty epididymal duct and rare mature sperms.Severe spermatogenic failure occurred,which did not recover after 30 d convalescence.Compared with the normal control group,the secretion of LH,FSH,and T in GTW 37.8 and 94.5 mg·kg^-1 groups was significantly decreased on d60（P〈0.01）.The expression of AR in the hypothalamus on d60 and d90,and in the testis and epididymis on d60,d90 and d120 was significantly decreased（P〈0.01）.CONCLUSION GTW causes obvious damage to the male genital organs.The toxicity of

关 键 词：雷公藤多苷 生殖器官 下丘脑-垂体-性腺轴 

分 类 号：R285.1[医药卫生—中药学]