白消安诱导雄性高促性腺激素性性腺功能减退症小鼠模型的构建  

Mouse Model Establishment of Male Hypergonadotropic Hypogonadism Induced by Busulfan

作　　者：许红秀 王苗苗 陈耀平[2] XU Hongxiu;WANG Miaomiao;CHEN Yaoping(Ningxia Medical University,Yinchuan 750004,China;General Hospital of Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学,银川750004 [2]宁夏医科大学总医院,银川750004

出　　处：《宁夏医科大学学报》2023年第5期445-450,468,共7页Journal of Ningxia Medical University

基　　金：国家自然科学基金项目(81760267)。

摘　　要：目的 研究雄性高促性腺激素性性腺功能减退症的机制,构建一种雄性高促性腺激素性性腺功能减退症小鼠模型。方法 将20只ICR雄性小鼠分为3组,对照组6只,实验组分3 mg·kg^(-1)×10 d组7只,4 mg·kg^(-1)×10 d组7只。对照组给予二甲基亚砜与生理盐水等量混合后腹腔注射,实验组给予白消安溶于二甲基亚砜与生理盐水等量混合液后腹腔注射,连续注射10 d。给药40 d后,取眼球血采用ELISA法检测血清性激素水平,取双侧睾丸称重,右侧睾丸分析精子数量及活力,左侧睾丸苏木精-伊红染色检测睾丸病理状态、睾丸病理评分、曲细精管直径和生精上皮厚度。结果 与对照组相比,4 mg·kg^(-1)×10 d组小鼠睾丸系数降低(P<0.05),体质量差异无统计学意义(P>0.05),证明此造模方法不会影响小鼠正常生长及发育。4 mg·kg^(-1)×10 d组睾丸Johnson评分低于对照组(P<0.05)。4 mg·kg^(-1)×10 d组精子数量低于对照组且低于3 mg·kg^(-1)×10 d组(P均<0.05),4 mg·kg^(-1)×10 d组多为Ⅳ级精子,活动能力极差。4 mg·kg^(-1)×10 d组曲细精管直径和生精上皮厚度低于对照组(P均<0.05)。4 mg·kg^(-1)×10 d组卵泡刺激素(FSH)、黄体生成素(LH)浓度高于对照组(P均<0.05),同时4 mg·kg^(-1)×10 d组睾酮浓度低于对照组(P<0.05)。睾丸HE染色显示4 mg·kg^(-1)×10 d组小鼠生精功能严重障碍,生精小管散在分布于间质中,间质细胞减少,生精小管上皮内细胞层数较少,各级生精细胞数量较少,管腔空洞,无成熟精子。结论 通过白消安小剂量持续刺激法腹腔注射成功构建了雄性高促性腺激素性性腺功能减退症小鼠模型。Objective To investigate the mechanism of male hypergonadotropic hypogonadism and construct a mouse model of male hypergonadotropic hypogonadism.Methods Twenty male ICR mice were divided into three groups,control group(6 mice),3 mg·kg^(-1)×10 d group(7 mice)and 4 mg·kg^(-1)×10 d group(7 mice)in the experimental group.The control group was given dimethyl sulfoxide mixed with normal saline and injected intraperitoneally,while the experimental group was given dimethyl sulfoxide mixed with normal saline and injected intraperitoneally for 10 consecutive days.After 40 days of administration,the blood serum sex hormone levels were measured by ELISA,both testis were weighed,sperm count and motility were analyzed in the right testis,and pathological status,pathological score,diameter of convoluted spermatogenic duct and thickness of spermatogenic epithelium were detected by hematoxylin-eosin staining in the left testis.Results Compared with the control group,the testis coefficient of the mice in the 4 mg·kg^(-1)×10 d group was decreased(P<0.05),and there was no significant difference in body weight(P>0.05),which proved that this modeling method did not affect the normal growth and development of the mice.The Johnson score of testis in the 4 mg·kg^(-1)×10 d group was significantly lower than that in the control group(P<0.05).The sperm count of the 4 mg·kg^(-1)×10 d group was significantly lower than that of the control group and that of the 3 mg·kg^(-1)×10 d group(P all<0.05),and most of the 4 mg·kg^(-1)×10 d group had gradeⅣsperm with extremely poor motility.The diameter of seminiferous tubules and the thickness of seminiferous epithelium in the 4 mg·kg^(-1)×10 d group were significantly lower than those in the control group(P all<0.05),and the spermatogenic function was severely impaired.The concentrations of follicle stimulating hormone(FSH)and luteinizing hormone(LH)in the 4 mg·kg^(-1)×10 d group were higher than those in the control group(P all<0.05),while the concentration of testosterone in the 4

关 键 词：高促性腺激素性性腺功能减退症 白消安 二甲基亚砜 睾丸 动物模型 小鼠 

分 类 号：R689.2[医药卫生—骨科学]