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时相依赖性下降的簇集蛋白作为潜在的耐药性癫痫的脑脊液生物标志物。

Time-dependent decrease of clusterin as a potential cerebrospinal fluid biomarker for drug-resistant epilepsy.

机构信息

Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016, China.

出版信息

J Mol Neurosci. 2014 Sep;54(1):1-9. doi: 10.1007/s12031-014-0237-3. Epub 2014 Feb 2.

Abstract

Our previous study on proteomic analysis has shown that clusterin (CLU) is significantly decreased in the cerebrospinal fluid (CSF) of patients with epilepsy. Therefore, the present study aimed to confirm CLU concentration reduction in the CSF of patients with drug-resistant epilepsy and drug-responsive epilepsy. Fifty-two patients with epilepsy (23 drug resistance and 29 drug effectivity) and 20 control individuals were recruited. The concentrations of CSF and serum CLU were detected. Moreover, alteration of CLU was detected in the rat hippocampus over time after pilocarpine-induced status epilepticus (SE). Our results showed that human CSF-CLU levels were decreased in patients with both drug-resistant epilepsy and drug-responsive epilepsy compared to controls, and concentration of CSF-CLU was obviously lower in drug-resistant epilepsy than in drug-responsive epilepsy. In the pilocarpine-induced seizure rats, expression of neuronal CLU was gradually decreased in a time-dependent manner from acute phase to chronic phase after the onset of SE. In conclusion, CLU level is decreased in the CSF of human epilepsy and the similar alteration is confirmed in a rat model with epilepsy. Therefore, CLU might contribute to the development of epilepsy and be a potential CSF biomarker for resistant epilepsy.

摘要

我们之前的蛋白质组学分析研究表明,簇蛋白(CLU)在癫痫患者的脑脊液(CSF)中显著减少。因此,本研究旨在确认耐药性癫痫和反应性癫痫患者 CSF 中 CLU 浓度降低。招募了 52 名癫痫患者(23 名耐药和 29 名有效)和 20 名对照者。检测 CSF 和血清 CLU 的浓度。此外,还检测了匹罗卡品诱导的癫痫持续状态(SE)后大鼠海马中 CLU 的时间变化。我们的结果表明,与对照组相比,耐药性癫痫和反应性癫痫患者的人 CSF-CLU 水平均降低,耐药性癫痫患者的 CSF-CLU 浓度明显低于反应性癫痫患者。在匹罗卡品诱导的癫痫大鼠中,自 SE 发作后的急性期到慢性期,神经元 CLU 的表达呈时间依赖性逐渐降低。总之,CLU 水平在人类癫痫患者的 CSF 中降低,在癫痫大鼠模型中也证实了类似的变化。因此,CLU 可能有助于癫痫的发展,并成为耐药性癫痫的潜在 CSF 生物标志物。

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