Bertlich Mattis, Ihler Friedrich, Weiss Bernhard G, Freytag Saskia, Strupp Michael, Canis Martin
*Department of Otorhinolaryngology-Head and Neck Surgery, University Medical Center Göttingen, Göttingen, Germany †Population Health and Immunity Division, Walter and Eliza Hall Institute ‡Department of Medical Biology, University of Melbourne, Parkville, Australia §Department of Neurology, Munich University Hospital, Munich, Germany.
Otol Neurotol. 2017 Dec;38(10):e545-e550. doi: 10.1097/MAO.0000000000001523.
The aim of this work was to evaluate the effect of tumor necrosis factor (TNF) and its neutralization with etanercept on the capability of cochlear pericytes to alter capillary diameter in the stria vascularis.
Twelve Dunkin-Hartley guinea pigs were randomly assigned to one of three groups. Each group was treated either with placebo and then placebo, TNF and then placebo, or TNF and then etanercept. Cochlear pericytes were visualized using diaminofluorescein-2-diacetate and intravasal blood flow by fluorescein-dextrane. Vessel diameter at sites of pericyte somas and downstream controls were quantified by specialized software. Values were obtained before treatment, after first treatment with tumor necrosis factor or placebo and after second treatment with etanercept or placebo.
Overall, 199 pericytes in 12 animals were visualized. After initial treatment with TNF, a significant decrease in vessel diameter at sites of pericyte somas (3.6 ±4.3%, n = 141) compared with placebo and downstream controls was observed. After initial treatment with TNF, the application of etanercept caused a significant increase (3.3 ±5.5%, n = 59) in vessel diameter at the sites of pericyte somata compared with placebo and downstream controls.
We have been able to show that cochlear pericytes are capable of reducing capillary diameter after exposition to TNF. Moreover, the reduction in capillary diameter observed after the application of TNF is revertible after neutralization of tumor necrosis factor by the application of etanercept. It seems that contraction of cochlear pericytes contributes to the regulation of cochlear blood flow.
本研究旨在评估肿瘤坏死因子(TNF)及其与依那西普中和对耳蜗周细胞改变血管纹毛细血管直径能力的影响。
将12只Dunkin-Hartley豚鼠随机分为三组。每组分别接受安慰剂然后安慰剂、TNF然后安慰剂或TNF然后依那西普治疗。使用二氨基荧光素-2-二乙酸盐观察耳蜗周细胞,用荧光素-葡聚糖观察血管内血流。通过专门软件对周细胞胞体部位及下游对照部位的血管直径进行量化。在治疗前、首次用肿瘤坏死因子或安慰剂治疗后以及第二次用依那西普或安慰剂治疗后获取数据。
总体而言,观察了12只动物中的199个周细胞。首次用TNF治疗后,与安慰剂及下游对照相比,周细胞胞体部位的血管直径显著减小(3.6±4.3%,n = 141)。首次用TNF治疗后,与安慰剂及下游对照相比,应用依那西普导致周细胞胞体部位的血管直径显著增加(3.3±5.5%,n = 59)。
我们已经能够证明,耳蜗周细胞在暴露于TNF后能够减小毛细血管直径。此外,应用TNF后观察到的毛细血管直径减小在用依那西普中和肿瘤坏死因子后是可逆的。耳蜗周细胞的收缩似乎有助于耳蜗血流的调节。