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紫杉醇应用于体内小鼠模型时微循环功能障碍的动力学

The Kinetics of Microcirculatory Dysfunction During Paclitaxel Application in an In Vivo Mouse Model.

作者信息

Reuter Susanne, Bajorat Rika, Müller-Graf Fabian, Zitzmann Amelie R, Böhm Stephan H, Reuter Daniel A, Vollmar Brigitte

机构信息

Institute for Experimental Surgery, University Medical Center Rostock, Schillingallee 69a, 18057 Rostock, Germany.

Department of Gynecology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.

出版信息

J Clin Med. 2025 Jul 8;14(14):4815. doi: 10.3390/jcm14144815.

Abstract

: Chemotherapy-induced peripheral neuropathy often has a lasting impact on the quality of life without existing causal treatment options. The aim of this study was to systematically investigate the temporal occurrence of paclitaxel-induced peripheral microcirculatory dysfunction. : Thirty-one female SKH-1 mice received six cycles of paclitaxel intraperitoneally in the treatment group and six cycles of saline in the control group. Intravital fluorescence analyses were performed in the groups 180 min after saline administration and immediately, 60 min, 120 min, and 180 min after paclitaxel administration to evaluate the effects on microcirculation and inflammation. : In addition to signs of systemic inflammation, the intravital microscopy revealed a marked reduction in functional capillary density, increased venous leukocyte adhesion, and endothelial permeability that persisted for at least three hours in paclitaxel-treated mice. : Our results show that paclitaxel-induced microcirculatory disturbances manifest immediately after application and last at least for 3 h. This suggests that options for prevention or at least amelioration could potentially be most effective if initiated parallel to the induction of chemotherapy and continued for a prolonged period of at least 3 h. Whether and to what extent the prolongation of the preventive strategies influences CIPN in the long term needs to be studied further.

摘要

化疗引起的周围神经病变常常对生活质量产生持久影响,且目前尚无有效的因果治疗方案。本研究旨在系统地研究紫杉醇诱导的外周微循环功能障碍的发生时间。31只雌性SKH-1小鼠,治疗组腹腔注射六个周期的紫杉醇,对照组腹腔注射六个周期的生理盐水。在注射生理盐水180分钟后以及注射紫杉醇后即刻、60分钟、120分钟和180分钟对两组进行活体荧光分析,以评估对微循环和炎症的影响。除全身炎症迹象外,活体显微镜检查显示,在接受紫杉醇治疗的小鼠中,功能性毛细血管密度显著降低、静脉白细胞粘附增加以及内皮通透性增加,且这种情况持续至少三小时。我们的结果表明,紫杉醇诱导的微循环紊乱在应用后即刻出现,并持续至少3小时。这表明,如果在化疗诱导的同时开始并持续至少3小时的较长时间,预防或至少改善的方案可能最有效。预防性策略的延长在长期内是否以及在多大程度上影响化疗引起的周围神经病变尚需进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b90/12295678/dd19901bdec5/jcm-14-04815-g001.jpg

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