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一氧化氮和精氨酸酶在急性神经炎症发病机制中的重要性:它们是朝着相同方向的相反作用者吗?

The importance of nitric oxide and arginase in the pathogenesis of acute neuroinflammation: are those contra players with the same direction?

作者信息

Ljubisavljevic Srdjan, Stojanovic Ivana, Pavlovic Radmila, Pavlovic Dusica

机构信息

Clinic of Neurology, Clinical Center Nis, Bul. Dr Zorana Djindjica 48, 18000, Nis, Serbia,

出版信息

Neurotox Res. 2014 Nov;26(4):392-9. doi: 10.1007/s12640-014-9470-3. Epub 2014 Apr 26.

DOI:10.1007/s12640-014-9470-3
PMID:24770974
Abstract

To investigate the concentrations of nitric oxide (NO) products (NOx) and arginase activity in acute neuroinflammation, we analyzed cerebrospinal fluid (CSF) and plasma of clinically isolated syndrome (CIS) and relapsing remitting multiple sclerosis (RRMS) patients, who were divided into groups on the basis of clinical and radiological disease activity. The NOx levels, in both, CSF and plasma, were increased in CIS (p = 0.0015, p = 0.0014, respectively) and RRMS group (p = 0.002, p = 0.0019, respectively), while arginase activity approached low levels, in CIS (p = 0.009, p = 0.02, respectively) and RRMS group (p = 0.018, p = 0.034, respectively) compared to controls. The NOx levels were higher in CSF and plasma of CIS than in RRMS group (p = 0.065, p = 0.037, respectively), inverse to arginase activity which was higher, in CSF and plasma, in RRMS than in CIS group (p = 0.031, p = 0.02, respectively). The CSF and plasma NOx values positively correlated with the clinical disease activity in CIS (r = 0.09, p = 0.81; r = 0.45, p = 0.023, respectively) and RRMS group (r = 0.311, p = 0.04; r = 0.512, p = 0.01, respectively). Also, CSF and plasma arginase activity showed negative correlation with clinical disease activity in CIS (r = 0.39, p = 0.03; r = 0.1, p = 0.65, respectively) and RRMS group (r = 0.43, p = 0.03; r = 0.62, p = 0.015, respectively). The CSF NOx levels showed positive correlation with volume of acute radiological lesions of CNS in CIS (r = 0.25, p = 0.045) and RRMS group (r = 0.31, p = 0.04), while arginase activity showed the negative correlations in CIS (r = 0.41; p = 0.035) and RRMS group (r = 0.52, p = 0.022). The results support NO and arginase involvement in the pathogenesis of acute neuroinflammation, which determination may be useful as surrogate markers for clinical and radiological disease activity.

摘要

为研究急性神经炎症中一氧化氮(NO)产物(NOx)的浓度及精氨酸酶活性,我们分析了临床孤立综合征(CIS)和复发缓解型多发性硬化症(RRMS)患者的脑脊液(CSF)和血浆,这些患者根据临床和影像学疾病活动情况被分组。CIS组(分别为p = 0.0015,p = 0.0014)和RRMS组(分别为p = 0.002,p = 0.0019)的CSF和血浆中NOx水平均升高,而与对照组相比,CIS组(分别为p = 0.009,p = 0.02)和RRMS组(分别为p = 0.018,p = 0.034)的精氨酸酶活性接近低水平。CIS组CSF和血浆中的NOx水平高于RRMS组(分别为p = 0.065,p = 0.037),与精氨酸酶活性相反,RRMS组CSF和血浆中的精氨酸酶活性高于CIS组(分别为p = 0.031,p = 0.02)。CIS组(分别为r = 0.09,p = 0.81;r = 0.45,p = 0.023)和RRMS组(分别为r = 0.311,p = 0.04;r = 0.512,p = 0.01)中,CSF和血浆NOx值与临床疾病活动呈正相关。此外,CIS组(分别为r = 0.39,p = 0.03;r = 0.1,p = 0.65)和RRMS组(分别为r = 0.43,p = 0.03;r = 0.62,p = 0.015)中,CSF和血浆精氨酸酶活性与临床疾病活动呈负相关。CIS组(r = 0.25,p = 0.045)和RRMS组(r = 0.31,p = 0.04)中,CSF NOx水平与中枢神经系统急性影像学病变体积呈正相关,而CIS组(r = 0.41;p = 0.035)和RRMS组(r = 0.52,p = 0.022)中,精氨酸酶活性呈负相关。这些结果支持NO和精氨酸酶参与急性神经炎症的发病机制,其测定可能作为临床和影像学疾病活动的替代标志物。

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