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摇头丸对斯普拉格-道利大鼠毒性的性别差异。

Sex differences in MDMA-induced toxicity in Sprague-Dawley rats.

作者信息

Soleimani Asl Sara, Mehdizadeh Mehdi, Hamedi Shahraki Soudabeh, Artimani Tayebeh, Joghataei Mohammad Taghi

出版信息

Funct Neurol. 2015 Apr-Jun;30(2):131-7. doi: 10.11138/fneur/2015.30.2.131.

DOI:10.11138/fneur/2015.30.2.131
PMID:26415786
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4610761/
Abstract

Recent evidence demonstrates that female subjects show exaggerated responses to 3,4-methylenedioxymethamphetamine (MDMA) compared with males. The aim of our study was to evaluate sex differences and the role of endogenous gonadal hormones on the effects of MDMA. Fifty-six intact and gonadectomized male and female Sprague-Dawley rats were randomly assigned to either MDMA (5 mg/kg) or saline treatment. Learning and memory were assessed using the Morris water maze (MWM). The expression of Bax and Bcl-2 in the hippocampus was detected by Western blotting. Behavioral analysis showed that MDMA led to memory impairment in both male and female rats. The female rats showed more sensitivity to impairment than the males, as assessed using all the memory parameters in the MWM. Ovariectomy attenuated the MDMA-induced memory impairment. By contrast, orchiectomized rats showed more impairment than MDMA-treated intact male rats. Bcl-2 and Bax were down-regulated and up-regulated in MDMA-treated male and female rats, respectively. MDMA treatment in the orchiectomized rats led to upregulation of Bax and down-regulation of Bcl-2. Ovariectomy attenuated the MDMA-induced up-regulation of Bax and caused more expression of Bcl-2 compared with what was observed in the MDMA-treated intact female rats. In summary, female rats showed exaggerated responses to the effects of MDMA and this may be explained by endogenous gonadal hormones.

摘要

最近的证据表明,与男性相比,女性受试者对3,4-亚甲基二氧甲基苯丙胺(摇头丸)的反应更为强烈。我们研究的目的是评估性别差异以及内源性性腺激素在摇头丸作用中的作用。将56只完整的和去势的雄性和雌性Sprague-Dawley大鼠随机分为摇头丸(5mg/kg)组或生理盐水处理组。使用莫里斯水迷宫(MWM)评估学习和记忆能力。通过蛋白质免疫印迹法检测海马中Bax和Bcl-2的表达。行为分析表明,摇头丸导致雄性和雌性大鼠的记忆障碍。使用MWM中的所有记忆参数评估,雌性大鼠比雄性大鼠对损伤更敏感。卵巢切除术减轻了摇头丸诱导的记忆障碍。相比之下,去势大鼠比接受摇头丸治疗的完整雄性大鼠表现出更多的损伤。在接受摇头丸治疗的雄性和雌性大鼠中,Bcl-2和Bax分别下调和上调。在去势大鼠中进行摇头丸治疗导致Bax上调和Bcl-2下调。与接受摇头丸治疗的完整雌性大鼠相比,卵巢切除术减轻了摇头丸诱导的Bax上调并导致Bcl-2表达增加。总之,雌性大鼠对摇头丸的作用表现出更强烈的反应,这可能由内源性性腺激素解释。

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