PO.ET06.06 · 实验与分子治疗
紫杉醇诱导的化疗性脱发大鼠模型
A paclitaxel-induced rat model of chemotherapy-induced alopecia
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
化疗性脱发(CIA)是癌症治疗中最显而易见且令人痛苦的毒性之一,对乳腺癌和卵巢癌女性患者的影响尤为突出,而紫杉醇仍是这类癌症的基石性治疗药物。尽管紫杉醇被广泛应用,但目前尚无标准化的动物模型用于研究紫杉醇诱导的脱发或评估保护策略。在此,我们报告首个可重复的紫杉醇诱导脱发大鼠模型。14日龄的Sprague-Dawley大鼠被随机分为对照组(n = 20)、低剂量紫杉醇组(n = 10)或高剂量紫杉醇组(n = 10),连续三天皮下给药。每日监测动物,脱发在两周后达到高峰。脱发严重程度由盲法评估者采用五分位分级量表(0 = 无脱发,4 = 完全脱发)进行评级。记录安全性终点(体重、梳理行为、活动)。第28天处死动物,从每组取一份代表性活检样本,经福尔马林固定、石蜡包埋并进行H&E染色。脱发严重程度在各治疗组间存在显著差异(p < 0.0001,Kruskal-Wallis检验)。脱发评分中位数在对照组为3,在低剂量紫杉醇组为1(p = 0.0015,Dunn事后检验),在高剂量紫杉醇组为1(p < 0.0001),两个紫杉醇剂量组之间无显著差异。皮肤镜检查显示注射部位(内侧臀部)出现局限性脱发。组织病理学显示毛囊密度降低及毛囊微小化,与经典CIA表现一致。紫杉醇给药可可靠地诱导出局限性脱发,重现了CIA的关键临床和组织学特征。这是首个标准化的紫杉醇CIA大鼠模型,填补了临床前皮肤病学与肿瘤学研究中的一项关键空白。该模型为机制研究和治疗测试提供了一个具有生物学相关性的平台,尤其适用于女性患者——对她们而言,脱发带来沉重的心理社会负担,并可能影响治疗依从性。
查看英文原文 English abstract
Chemotherapy-induced alopecia (CIA) is one of the most visible and distressing toxicities of cancer therapy, disproportionately affecting women with breast and ovarian cancers, where paclitaxel remains a cornerstone treatment. Despite its widespread use, no standardized animal model exists to study paclitaxel-induced alopecia or evaluate protective strategies. Here, we report the first reproducible rat model of paclitaxel-induced alopecia. Fourteen-day-old Sprague-Dawley rats were randomized to control (n = 20), low-dose paclitaxel (n = 10), or high-dose paclitaxel (n = 10), administered subcutaneously for three consecutive days. Animals were monitored daily, with peak alopecia observed after two weeks. Alopecia severity was graded by blinded assessors using a quintile grading scale (0 = no hair loss, 4 = complete alopecia). Safety endpoints (weight, grooming, activity) were recorded. On day 28, animals were euthanized and a representative biopsy from each group was acquired, formalin-fixed, paraffin-embedded, and stained with H&E. Alopecia severity differed significantly across treatment groups (p < 0.0001, Kruskal-Wallis). Median alopecia scores were 3 in controls, 1 in low-dose paclitaxel (p = 0.0015, Dunn's post hoc), and 1 in high-dose paclitaxel (p < 0.0001), with no significant difference between paclitaxel doses. Dermoscopy demonstrated localized alopecia at the medial rump injection site. Histopathology revealed reduced follicular density and follicular miniaturization, consistent with classical CIA. Paclitaxel administration reliably induced localized alopecia replicating key clinical and histologic features of CIA. This represents the first standardized paclitaxel rat model of CIA and addresses a critical gap in preclinical dermatology and oncology research. This model provides a biologically relevant platform for mechanistic studies and therapeutic testing, particularly relevant to women, for whom alopecia carries substantial psychosocial burden and may influence treatment adherence.
利益披露 Disclosure
S. I. Gaumond, None.