规律性自愿的跑步与小鼠的肿瘤血管化和免疫细胞浸润增加以及肿瘤生长减少有关。
Regular Voluntary Running is Associated with Increased Tumor Vascularization and Immune Cell Infiltration and Decreased Tumor Growth in Mice.
发表日期：2023 Mar 17
作者：
Mário Esteves, Carina Silva, António Bovolini, Sofia S Pereira, Tiago Morais, Ângela Moreira, Madalena M Costa, Mariana P Monteiro, Jose Alberto Duarte
来源：
BIOMEDICINE & PHARMACOTHERAPY
摘要：
肿瘤的血管功能紊乱会限制血液灌注，阻碍免疫细胞的输送。我们旨在调查是否定期自愿慢跑有利于促进肿瘤血管重构，提高肿瘤内免疫细胞浸润并抑制肿瘤生长。我们在C57BL/6雄性小鼠（n = 28）的背部皮下注射RM1细胞悬液（1.5×105细胞/500µL PBS）诱导肿瘤，并随机分为两组：静态组（n = 14）和自愿跑步组（n = 14）。每组中的七只小鼠在细胞接种后的14天和28天牺牲，以评估肿瘤重量、微血管密度、血管腔规则性和肿瘤内NKG2D受体、CD4 +和CD8 + T细胞的数量，通过免疫组织化学方法。统计学推断通过双因素方差分析进行。在经过轮式运动的小鼠中，肿瘤在14天（0.17±0.1g vs. 0.48±0.2g，p <0.05）和28天（0.92±0.7g vs. 2.09±1.3g，p <0.05）时呈较小体积，微血管密度较高（21.20±3.2 vs. 15.86±4.0个/视野，p <0.05），血管腔规则性更好（1.06±0.2 vs. 1.43±0.2，p <0.05），并且在28天后CD8 + T细胞数量更多（464.95±48.0 vs. 364.70±49.4个/mm2，p <0.01）。在14天（263.27±25.8个/mm2，p <0.05）和28天（295.06±56.2个/mm2，p <0.001）时，自愿跑步的小鼠中NKG2D表达增加。在小鼠中，定期自愿慢跑可以调节肿瘤血管，增加免疫细胞浸润并减缓肿瘤生长。Thieme版权所有。
Tumors present dysfunctional vasculature that limits blood perfusion and hinders immune cells delivery. We aimed to investigate if regular voluntary running promotes tumor vascular remodelling, improves intratumoral immune cells infiltration and inhibits tumor growth. Tumors were induced in C57BL/6 male mice (n=28) by subcutaneous inoculation in the dorsal region with a suspension of RM1 cells (1.5×105 cells/500 µL PBS) and randomly allocated into two groups: sedentary (n=14) and voluntarily exercised on a wheel (n=14). Seven mice from each group were sacrificed 14 and 28 days after cells' inoculation to evaluate tumor weight, microvessel density, vessels' lumen regularity and the intratumoral quantity of NKG2D receptors, CD4+and CD8+T cells, by immunohistochemistry. The statistical inference was done through a two-way ANOVA. Exercised mice developed smaller tumors at 14 (0.17±0.1 g vs. 0.48±0.2 g, p<0.05) and 28 (0.92±0.7 g vs. 2.09±1.3 g, p<0.05) days, with higher microvessel density (21.20±3.2 vs. 15.86±4.0 vessels/field, p<0.05), more regular vessels' lumen (1.06±0.2 vs. 1.43±0.2, p<0.05), and higher CD8+T cells (464.95±48.0 vs. 364.70±49.4 cells/mm2, p<0.01), after 28 days. NKG2D expression was higher in exercised mice at 14 (263.27±25.8 cells/mm2, p<0.05) and 28 (295.06±56.2 cells/mm2, p<0.001) days. Regular voluntary running modulates tumor vasculature, increases immune cells infiltration and attenuates tumor growth, in mice.Thieme. All rights reserved.