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在关节炎患者的人类滑膜和小鼠淋巴结周围代谢活跃的脂肪组织中,交感神经纤维密度增加。

Increased density of sympathetic nerve fibers in metabolically activated fat tissue surrounding human synovium and mouse lymph nodes in arthritis.

作者信息

Straub Rainer H, Lowin Torsten, Klatt Susanne, Wolff Christine, Rauch Luise

机构信息

University Hospital Regensburg, Regensburg, Germany.

出版信息

Arthritis Rheum. 2011 Nov;63(11):3234-42. doi: 10.1002/art.30516.

DOI:10.1002/art.30516
PMID:21702024
Abstract

OBJECTIVE

To investigate the density of sympathetic nerve fibers in and the metabolic activation of fat tissue surrounding human synovium in rheumatoid arthritis (RA)/osteoarthritis (OA) and in the draining lymph nodes of arthritic and normal mice.

METHODS

Using immunofluorescence and immunohistochemistry, the density of sympathetic nerve fibers and the presence of nerve repellent factors were investigated. The metabolic activation of fat tissue was estimated by the occurrence of small-vacuole adipocytes, expression of β3-adrenoceptors, and adipose tissue weight.

RESULTS

The density of sympathetic nerve fibers was markedly increased in fat tissue surrounding RA synovium compared with that in fat tissue surrounding OA synovium. In adipose tissue adjacent to draining lymph nodes, the density of sympathetic nerve fibers was higher in arthritic mice compared with normal mice. In human synovium and mouse draining lymph nodes, the 2 sympathetic nerve repellent factors, semaphorin 3C and semaphorin 3F, were highly expressed. In arthritic compared with normal mice, the fat tissue around lymph nodes was markedly lighter, adipocytes had more fragmented lipid droplets, and fat tissue demonstrated high expression of β3-adrenoceptors.

CONCLUSION

This study demonstrated an increased density of sympathetic nerve fibers in metabolically activated fat tissue surrounding human RA synovium and the draining lymph nodes of arthritic mice. Because sympathetic neurotransmitters stimulate lipolysis, the repulsion of sympathetic nerve fibers from inflamed regions and their increased occurrence in fat tissue probably represent an adaptive program to support the proinflammatory process by releasing energy-rich substrates.

摘要

目的

研究类风湿关节炎(RA)/骨关节炎(OA)患者滑膜周围脂肪组织以及关节炎小鼠和正常小鼠引流淋巴结中交感神经纤维的密度及其代谢激活情况。

方法

采用免疫荧光和免疫组织化学方法,研究交感神经纤维的密度及神经排斥因子的存在情况。通过小泡脂肪细胞的出现、β3-肾上腺素能受体的表达及脂肪组织重量来评估脂肪组织的代谢激活情况。

结果

与OA滑膜周围脂肪组织相比,RA滑膜周围脂肪组织中交感神经纤维的密度显著增加。在引流淋巴结附近的脂肪组织中,关节炎小鼠的交感神经纤维密度高于正常小鼠。在人类滑膜和小鼠引流淋巴结中,两种交感神经排斥因子,即信号素3C和信号素3F,高表达。与正常小鼠相比,关节炎小鼠淋巴结周围的脂肪组织明显更轻,脂肪细胞的脂滴更破碎,且脂肪组织中β3-肾上腺素能受体高表达。

结论

本研究表明,人类RA滑膜周围及关节炎小鼠引流淋巴结中代谢激活的脂肪组织中交感神经纤维密度增加。由于交感神经递质刺激脂肪分解,交感神经纤维从炎症区域的排斥及其在脂肪组织中出现的增加可能代表一种适应性程序,通过释放富含能量的底物来支持促炎过程。

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