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氯胺酮通过破坏下丘脑-垂体-睾丸轴对生殖系统的毒性作用。

Toxic effects of ketamine on reproductive system via disrupting hypothalamic-pituitary-testicular axis.

机构信息

Department of Anesthesiology, Jinan Maternity and Child Care Hospital, Jinan, China.

出版信息

Eur Rev Med Pharmacol Sci. 2017 Apr;21(8):1967-1973.

Abstract

OBJECTIVE

In this paper, we focused on the toxic effect of ketamine on the reproductive system in male rats and its underlying mechanisms.

MATERIALS AND METHODS

Rats were randomly allocated into four groups (n=10), i.e. a control group and 3 ketamine groups (high-dose, mid-dose, low-dose). Animals in the ketamine groups received an intraperitoneal injection of ketamine (20, 40 or 60 mg/kg) every 3 days for 7 times. Control rats were injected with normal saline instead. To investigate the disruption potential on the hypothalamic-pituitary-testicular (HPG) axis, the relative hormone levels in serum and mRNA expressions for some reproduction-related genes in reproductive organs were evaluated.

RESULTS

Ketamine significantly decreased the serum concentrations of testosterone (T), inhibin B, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Meanwhile, the mRNA expressions of GnRH in the hypothalamus, GnRH receptor, LH-β and FSH-β in the pituitary, and LH receptor and FSH receptor in testes were also significantly inhibited by ketamine compared with the control (p<0.01).

CONCLUSIONS

These results demonstrated that the ketamine had a toxic effect on the reproductive system via breaking the HPG equilibrium.

摘要

目的

本文主要关注氯胺酮对雄性大鼠生殖系统的毒性作用及其潜在机制。

材料和方法

将大鼠随机分为四组(n=10),即对照组和 3 个氯胺酮组(高剂量组、中剂量组、低剂量组)。氯胺酮组大鼠每隔 3 天接受一次腹腔注射氯胺酮(20、40 或 60mg/kg),共 7 次。对照组大鼠注射生理盐水。为了研究对下丘脑-垂体-睾丸(HPG)轴的破坏潜力,评估了血清中相关激素水平以及生殖器官中某些与生殖相关基因的 mRNA 表达情况。

结果

氯胺酮显著降低了血清中睾酮(T)、抑制素 B、卵泡刺激素(FSH)和黄体生成素(LH)的浓度。同时,与对照组相比,氯胺酮还显著抑制了下丘脑 GnRH、垂体 GnRH 受体、LH-β和 FSH-β以及睾丸 LH 受体和 FSH 受体的 mRNA 表达(p<0.01)。

结论

这些结果表明,氯胺酮通过破坏 HPG 平衡对生殖系统具有毒性作用。

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