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氯胺酮与氯胺酮加乙醇处理后人及小鼠小脑下调。

Downregulation in the human and mice cerebella after ketamine versus ketamine plus ethanol treatment.

机构信息

Brain Research Centre, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.

出版信息

Microsc Res Tech. 2012 Mar;75(3):258-64. doi: 10.1002/jemt.21052. Epub 2011 Aug 1.

DOI:10.1002/jemt.21052
PMID:21809417
Abstract

To study the deleterious effects of ketamine and the potential interaction effects between ethanol and ketamine on the cerebellum, functional magnetic resonance imaging (fMRI) tests were performed on the habitual ketamine users (n = 3) when they flexed and extended their upper limbs. Another fMRI test was performed on the same participants in which they consumed alcohol (12%, 200 mL) 1 h before the test. Downregulation on the activity of cerebellum was observed and the level of activation in the cerebellum decreased dramatically in habitual ketamine users with alcohol consumption before the test. Further studies were performed by using male ICR mice receiving treatment of ketamine only [30 mg kg(-1) intraperitoneally (i.p.)] or ethanol only everyday (0.5 mL 12% orally) and those with coadministration of the above dosages of ketamine and ethanol for 3 months. Fewer Purkinje cells were observed in the cerebellar sections of ketamine treated mice under silver staining. For TUNEL test, a significant increase in the apoptotic cells were observed in the cerebella of the ketamine treated mice (P = 0.016) and of those with co-administration of ketamine and ethanol (P < 0.001), when compared with the control. A statistical significance (P < 0.001) in two-way ANOVA test indicated that there might be an interactive mechanism between ethanol and ketamine acting on the cerebellum.

摘要

为了研究氯胺酮的有害作用,以及乙醇和氯胺酮之间的潜在相互作用对小脑的影响,对习惯性氯胺酮使用者(n = 3)进行了功能磁共振成像(fMRI)测试,当他们弯曲和伸展上肢时。对同一参与者进行了另一次 fMRI 测试,他们在测试前 1 小时饮用了酒精(12%,200 mL)。在测试前饮酒的习惯性氯胺酮使用者中观察到小脑活动下调,小脑的激活水平显著降低。进一步的研究是通过对接受氯胺酮(30 mg kg(-1) 腹腔内(i.p.))或仅乙醇(0.5 mL 12% 口服)治疗的雄性 ICR 小鼠,以及同时给予上述剂量氯胺酮和乙醇治疗 3 个月的小鼠进行的。在银染小脑切片中,氯胺酮处理的小鼠中观察到较少的浦肯野细胞。在 TUNEL 试验中,与对照组相比,氯胺酮处理的小鼠(P = 0.016)和同时给予氯胺酮和乙醇的小鼠(P < 0.001)小脑的凋亡细胞显著增加。双向方差分析试验的统计学意义(P < 0.001)表明,乙醇和氯胺酮之间可能存在一种作用于小脑的相互作用机制。

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