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精神分裂症中单核细胞激活受损:超微结构异常与白细胞介素-1β产生增加。

Impaired monocyte activation in schizophrenia: ultrastructural abnormalities and increased IL-1β production.

作者信息

Uranova Natalya A, Bonartsev P D, Androsova L V, Rakhmanova V I, Kaleda V G

机构信息

Laboratory of Clinical Neuropathology, Mental Health Research Centre, Zagorodnoe Shosse 2, Moscow, 117152, Russia.

Laboratory of Neuroimmunology, Mental Health Research Centre, Zagorodnoe Shosse 2, Moscow, 117152, Russia.

出版信息

Eur Arch Psychiatry Clin Neurosci. 2017 Aug;267(5):417-426. doi: 10.1007/s00406-017-0782-1. Epub 2017 Mar 17.

Abstract

Monocyte activation is consistently reported in patients with schizophrenia (SZ). We aimed to study the ultrastructure of monocytes and monocyte production of IL-1β in drug-free patients with SZ and controls. Monocytes from young (18-30 y.o.) healthy and SZ men in relapse were studied. Electron microscopy and morphometry were applied to estimate areas of monocytes, volume density (Vv), areas, and number of organelles. The production IL-1β by monocytes was estimated by the ELISA method. Group differences were examined using ANCOVA. Pearson's correlation coefficients were used to examine the effects of possible confounding variables. Correlation analyses were applied to detect the relationships between the parameters of monocytes measured and between the parameters measured and the IL-1β production. Area of nucleolus, Vv and area of mitochondria and lysosomes, and the number of lysosomes were significantly increased in patients as compared to controls. Area of mitochondria was correlated significantly with Vv and area of lysosomes, and the number of lysosomes was significantly correlated with area of monocyte and Vv of vacuoles only in the control group. The production of IL-1β by monocytes was higher in patients than in controls (p = 0.01) and was correlated with Vv of lysosomes (r = 0.68, p = 0.04) and area of lysosomes (r = 0.78, p = 0.013). The data provide new evidence for over activation of monocytes in SZ and disturbed metabolic relationships between lysosomes, mitochondria, and vacuoles.

摘要

精神分裂症(SZ)患者中单核细胞活化现象一直有报道。我们旨在研究未用药的SZ患者及对照组中单核细胞的超微结构以及单核细胞产生白细胞介素-1β(IL-1β)的情况。对处于复发期的年轻(18 - 30岁)健康男性和SZ男性的单核细胞进行了研究。应用电子显微镜和形态计量学来估计单核细胞的面积、体积密度(Vv)、细胞器的面积和数量。通过酶联免疫吸附测定(ELISA)法估计单核细胞产生IL-1β的情况。使用协方差分析(ANCOVA)检验组间差异。采用Pearson相关系数检验可能的混杂变量的影响。进行相关分析以检测所测量的单核细胞参数之间以及所测量的参数与IL-1β产生之间的关系。与对照组相比,患者的核仁面积、线粒体和溶酶体的Vv及面积以及溶酶体数量显著增加。仅在对照组中,线粒体面积与Vv和溶酶体面积显著相关,溶酶体数量仅与单核细胞面积和液泡Vv显著相关。患者单核细胞产生IL-1β的水平高于对照组(p = 0.01),且与溶酶体的Vv(r = 0.68,p = 0.04)和溶酶体面积(r = 0.78,p = 0.013)相关。这些数据为SZ中单核细胞过度活化以及溶酶体、线粒体和液泡之间代谢关系紊乱提供了新证据。

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