中国药物警戒 ›› 2022, Vol. 19 ›› Issue (3): 248-251.
DOI: 10.19803/j.1672-8629.2022.03.04

• 基础与临床研究 • 上一篇    下一篇

小鼠大剂量糖皮质激素不良反应的性别差异性研究

卫克昭, 吴欢, 张子旭, 冯加华, 高建平*   

  1. 上海中医药大学中药学院,上海 201203
  • 收稿日期:2021-02-26 出版日期:2022-03-15 发布日期:2022-03-16
  • 通讯作者: *高建平,女,博士,副教授,药理毒理学研究和评价。E-mail:zydgjp@aliyun.com
  • 作者简介:卫克昭,女,硕士,药理毒理学研究和评价。
  • 基金资助:
    国家自然科学基金资助项目(82074055); 上海中医药大学预算内科研项目(2020LK016)

Gender differences in adverse reactions in high-dose glucocorticoids in mice

WEI Kezhao, WU Huan, ZHANG Zixu, FENG Jiahua, GAO Jianping*   

  1. School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • Received:2021-02-26 Online:2022-03-15 Published:2022-03-16

摘要: 目的 研究糖皮质激素大剂量用药对不同性别小鼠的整体状况、免疫器官及内分泌系统不良影响的差异。方法 将雌、雄小鼠分别随机分为对照组和氢化可的松组(50 mg·kg-1每次,每日2次),分别肌内注射生理盐水和氢化可的松注射液14 d,每3 d测定1次体重,停药7 d后测量体温、自主活动次数、负重力竭游泳时间,停药9 d后取血、分离免疫器官及性器官脏器并称重并计算其指数;采用硫代巴比妥酸法测定血清丙二醛,采用羟胺法测定血清超氧化物歧化酶活性,采用ELISA法测定雌性小鼠的雌二醇和雄性小鼠的睾酮水平。结果 与对照组相比,小鼠在注射氢化可的松4 d开始体重显著降低(P<0.05或P<0.01),其中雄性小鼠的体重降低更明显,停药后体重未见有恢复的趋势;氢化可的松组雄性小鼠游泳时间及自主活动次数明显减少(P<0.05),脾脏质量及其指数、睾丸指数较正常组显著增加(P<0.05或P<0.01),胸腺质量及其指数、附睾和前列腺质量及指数显著降低(P<0.05或P<0.01),肾上腺和精囊腺变化不明显;氢化可的松组雌性小鼠卵巢质量及其指数显著降低(P<0.05),脾脏、胸腺、肾上腺和子宫各脏器的质量及指数均未见明显变化。氢化可的松使雄性小鼠血清睾酮、雌性小鼠血清雌二醇水平稍有降低,但均无明显差异,对血清超氧化物歧化酶和丙二醛水平、体温未见有明显影响。结论 小鼠长期大剂量给予氢化可的松后,机体一般状况较差,免疫和内分泌器官异常,同时性激素分泌有减少的趋势,对雄性小鼠的整体影响较雌性小鼠更明显。

关键词: 糖皮质激素, 免疫器官, 内分泌器官, 性别差异性, 小鼠

Abstract: Objective To study the effects of high-dose glucocorticoid on the general condition, immune organs and endocrine system in mice of different sexes. Methods Male and female mice were randomly divided into control group and cortisol group (50 mg·kg-1 each time, 2 times/d), and were intramuscularly injected with saline or cortisol for 14 days, respectively. The body weight was measured once every 3 days throughout the experiment, and the body temperature, voluntary activity times and swimming time after 7 days off the medication were measured. After 9 days off the medication, blood samples were taken, immune organs and sexual organs were separated and weighed and then their indexes were calculated, MDA content was measured by TBA method, and SOD activity was measured by hydroxylamine method, estradiol level in female mice and testosterone level in male mice were measured by ELISA methods in serum. Results Compared with the control group, the weight of mice was significantly lower from the fourth day of intramuscular cortisol (P<0.05 or P<0.01), the male mice lost more weight than the female mice, and the weight of the male group did not recover after drug withdrawal of the cortisol group. The time of swimming and times of voluntary movement were significantly decreased (P<0.05), the spleen mass and its index, testis index of male mice were significantly increased (P<0.05 or P<0.01), the thymus mass and its index, epididymis and prostate mass and index were significantly decreased (P<0.05 or P<0.01), the adrenal gland and seminal vesicle were not significantly changed of male mice in the cortisol group. The ovary mass and its index were significantly decreased (P<0.05), the mass and index of spleen, thymus, adrenal gland and uterus were not significantly changed of female mice in the cortisol group. The level of serum testosterone in male mice and estradiol in female mice were slightly decreased by cortisol, but there was no significant difference between them. Conclusion After long-term high dose administration in mice, cortisol can affect the general condition of mice, cause abnormal immune and endocrine organs, and have a tendency to reduce the secretion of sex hormones, especially in male mice.

Key words: glucocorticoid, immune organs, endocrine organs, gender differences, mice

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