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复发缓解型多发性硬化症急性复发期与病情稳定期脑脊液中神经活性甾体的评估

Assessment of neuroactive steroids in cerebrospinal fluid comparing acute relapse and stable disease in relapsing-remitting multiple sclerosis.

作者信息

Orefice Ns, Carotenuto A, Mangone G, Bues B, Rehm R, Cerillo I, Saccà F, Calignano A, Orefice G

机构信息

Department of Pharmacy, "Federico II" University, Naples, Italy.

Department of Neurosciences, Reproductive Sciences and Odontostomatology, "Federico II" University, Naples, Italy.

出版信息

J Steroid Biochem Mol Biol. 2016 May;159:1-7. doi: 10.1016/j.jsbmb.2016.02.012. Epub 2016 Feb 15.

Abstract

Previous studies have reported an involvement of neuroactive steroids as neuroprotective and anti-inflammatory agents in neurological disorders such as multiple sclerosis (MS); an analysis of their profile during a specific clinical phase of MS is largely unknown. The pregnenolone (PREG), dehydroepiandrosterone (DHEA), and allopregnanolone (ALLO) profile was evaluated in cerebrospinal fluid (CSF) in relapsing-remitting multiple sclerosis (RR-MS) patients as well as those in patients affected by non-inflammatory neurological (control group I) and without neurological disorders (control group II). An increase of PREG and DHEA values was shown in CSF of male and female RR-MS patients compared to those observed in both control groups. The ALLO values were significantly lower in female RR-MS patients than those found in male RR-MS patients and in female without neurological disorder. During the clinical relapse, we observed female RR-MS patients showing significantly increased PREG values compared to female RR-MS patients in stable phase, while their ALLO values showed a significant decrease compared to male RR-MS patients of the same group. Male RR-MS patients with gadolinium-enhanced lesions showed PREG and DHEA values higher than those found in female RR-MS patients with gadolinium-enhanced lesions. Similary, male RR-MS patients with gadolinium-enhanced lesions showed PREG and DHEA values higher than male without gadolinium-enhanced lesions. Female RR-MS patients with gadolinium-enhanced lesions showed DHEA values higher than those found in female RR-MS patients with gadolinium-enhanced lesions. Male and female RR-MS patients with gadolinium-enhanced lesions showed ALLO values higher than those found in respective gender groups without gadolinium-enhanced lesions. ALLO values were lower in male than in female RR-MS patients without gadolinium-enhanced lesions. Considering the pharmacological properties of neuroactive steroids and the observation that neurological disorders influence their concentrations, these endogenous compounds may have an important role as prognostic factors of the disease and used as markers of MS activity such as relapses.

摘要

先前的研究报道,神经活性甾体作为神经保护剂和抗炎剂参与了诸如多发性硬化症(MS)等神经系统疾病;而在MS特定临床阶段对其特征的分析在很大程度上尚不清楚。对复发缓解型多发性硬化症(RR-MS)患者以及非炎性神经系统疾病患者(对照组I)和无神经系统疾病患者(对照组II)的脑脊液(CSF)中的孕烯醇酮(PREG)、脱氢表雄酮(DHEA)和别孕烷醇酮(ALLO)特征进行了评估。与两个对照组相比,RR-MS男性和女性患者脑脊液中的PREG和DHEA值均有所升高。女性RR-MS患者的ALLO值显著低于男性RR-MS患者以及无神经系统疾病的女性。在临床复发期间,我们观察到女性RR-MS患者与稳定期女性RR-MS患者相比,PREG值显著升高,而其ALLO值与同组男性RR-MS患者相比显著降低。有钆增强病灶的男性RR-MS患者的PREG和DHEA值高于有钆增强病灶的女性RR-MS患者。同样,有钆增强病灶的男性RR-MS患者的PREG和DHEA值高于无钆增强病灶的男性。有钆增强病灶的女性RR-MS患者的DHEA值高于有钆增强病灶的女性RR-MS患者。有钆增强病灶的男性和女性RR-MS患者的ALLO值高于各自性别组中无钆增强病灶的患者。无钆增强病灶的男性RR-MS患者的ALLO值低于女性。考虑到神经活性甾体的药理特性以及神经系统疾病会影响其浓度这一观察结果,这些内源性化合物可能作为疾病的预后因素具有重要作用,并可作为MS活动(如复发)的标志物。

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