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[微循环系统、血管壁损伤标志物及风湿性疾病中该过程的系统性]

[System of microcirculation, markers of vascular wall damage and systematicity of the process in rheumatic diseases].

作者信息

Shilkina N P, Butusova S V, Driazhenkova I V

出版信息

Angiol Sosud Khir. 2014;20(1):27-34.

PMID:24722018
Abstract

The work was aimed at studying the interrelationship of the microcirculation system and the parameters of endothelial activation with markers of inflammatory process activity in rheumatic diseases (RD). We carried out a comprehensive examination of a total of 330 patients presenting with systemic diseases of connective tissue (SDCT), rheumatoid arthritis (RA) and systemic vasculitis (SV). Studying microcirculation included impregnation of filmy preparations according to the V.V. Kupriyanov technique and biomicroscopy of the conjunctiva of the eyeball. We also determined markers of endothelial activation and lesion of vascular wall, indices of activity of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and vasculitis clinical activity index (VCAI), common carotid artery intima-media thickness (CCA-IMT), biopsy materials of the musculocutaneous flap, of the operational and autopsy materials. Determining the indices of microcirculation showed that first of all the process involves postcapillaries and venules which are dilated, becoming tortuous, with the formation of microaneurysms and stellate venules. Capillaries, postcapillaries and venules were found to contain parietally located small-grained conglomerates of blood platelets and thrombocytic masses plugging up the lumens of microvessels. Intravascular alterations were characterized by the presence of erythrocyte aggregates, stases, microthrombovasculitis, «sludge» phenomenon, and a decrease in capillary blood flow. Extravascular changes included perivascular haemorrhages. In arterioles and precapillaries the inflammatory process manifested itself by swelling, dystrophy and desquamation of endothelial cells, plasmatic impregnation of the walls, luminal thrombosis followed by the development of severe sclerosis and glialinosis. The morphological study showed the presence of destructive alterations in the vascular wall, fibrinoid necrosis, and infiltration-proliferative cellular reaction. The most pronounced changes in the autoimmune inflammation markers had place in RA and systemic lupus erythematosus (SLE). We revealed increased indices of inflammatory process activity such as interleukin-8, C-reactive protein (CRP). We also revealed the signs of endothelial dysfunction, manifesting itself as a statistically significant (p<0.01) increase in concentrations of the soluble vascular cell adhesion molecule (sVCAM-1), von Willebrand factor antigen (VWFA), the number of desquamated endotheliocytes (DE). Also observed was a clear-cut dependence of the level of endothelial activation markers from the degree of the processes activity. We revealed a positive correlation between the level of CRP, IgG RF, the level of sVCAM-1 and the number of DE. The levels of interleukin-8, sVCAM-1 and VWFA were elevated in patients with RD. Increased activity of the disease was accompanied by impairments at the level of the microcirculatory bed, an increase in the concentration of inflammation markers and indices of endothelial dysfunction.

摘要

这项工作旨在研究风湿性疾病(RD)中微循环系统与内皮激活参数以及炎症过程活动标志物之间的相互关系。我们对总共330例患有结缔组织系统性疾病(SDCT)、类风湿性关节炎(RA)和系统性血管炎(SV)的患者进行了全面检查。研究微循环包括根据V.V.库普里亚诺夫技术对薄膜制剂进行浸染以及对眼球结膜进行生物显微镜检查。我们还测定了内皮激活和血管壁损伤的标志物、类风湿性关节炎(RA)、系统性红斑狼疮(SLE)的活动指数以及血管炎临床活动指数(VCAI)、颈总动脉内膜中层厚度(CCA-IMT)、肌皮瓣活检材料、手术和尸检材料。测定微循环指标显示,首先受累的是后微动脉和小静脉,它们扩张、迂曲,形成微动脉瘤和星状小静脉。发现毛细血管、后微动脉和小静脉内有位于血管壁的小颗粒状血小板聚集体和血栓块堵塞微血管腔。血管内改变的特征为存在红细胞聚集、血流淤滞、微血栓性血管炎、“淤泥”现象以及毛细血管血流减少。血管外改变包括血管周围出血。在小动脉和毛细血管前,炎症过程表现为内皮细胞肿胀、营养不良和脱屑,血管壁有血浆浸润,管腔内血栓形成,随后发展为严重的硬化和胶质化。形态学研究显示血管壁存在破坏性改变、纤维蛋白样坏死以及浸润性增殖性细胞反应。自身免疫性炎症标志物最明显的变化发生在RA和系统性红斑狼疮(SLE)中。我们发现炎症过程活动指数如白细胞介素-8、C反应蛋白(CRP)升高。我们还发现了内皮功能障碍的迹象,表现为可溶性血管细胞粘附分子(sVCAM-1)、血管性血友病因子抗原(VWFA)浓度以及脱屑内皮细胞数量在统计学上显著增加(p<0.01)。还观察到内皮激活标志物水平与疾病活动程度之间存在明显的相关性。我们发现CRP、IgG RF水平、sVCAM-1水平与脱屑内皮细胞数量之间呈正相关。RD患者白细胞介素-8、sVCAM-1和VWFA水平升高。疾病活动度增加伴随着微循环床水平的损害、炎症标志物浓度升高以及内皮功能障碍指标增加。

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