Data Sheet 5_Voluntary wheel running promotes lymphangiogenesis in slow-twitch muscle in young mice.docx

IntroductionLymphatic vessels contribute to tissue homeostasis. Although the lymphatic vessels in skeletal muscle are known to undergo structural changes under certain conditions, such as atrophy and injury, effects of exercise on intramuscular lymphatic vessels remain unclear.
MethodsThis study was aimed at investigating whether 8 weeks of voluntary wheel running (VWR) induces histological changes in lymphatic and blood capillaries, and whether these responses are related to age and myofiber type. Young (3-month-old) and aged (18-month-old) male C57BL/6 mice were assigned to sedentary or VWR groups. The soleus (SOL; slow-twitch) and plantaris (PLAN; fast-twitch) muscles were analyzed using immunohistochemistry and quantitative polymerase chain reaction.
ResultsIn young mice, VWR increased the quantity of type I myofibers and significantly enhanced the density of lymphatic vessels and blood capillaries in the SOL, besides upregulating the expression of vascular endothelial growth factors, VEGF-C and VEGF-D. These changes were not observed in aged mice or in the PLAN of mice in either age group.
DiscussionAlthough aged mice showed a similar increase in the quantity of type I myofibers, they did not exhibit corresponding vascular remodeling, which suggests that aging reduces responsiveness to exercise-induced angiogenic and lymphangiogenic signals. Overall, these findings indicate that VWR promotes lymphangiogenesis and angiogenesis in slow-twitch muscle in young mice, probably as an adaptive response to meet the increased oxygen demand. Exercise-induced vascular and lymphatic remodeling in skeletal muscle is significantly influenced by age and myofiber type, highlighting a reduced adaptive capacity of aged muscle that may impact strategies for promoting vascular health through physical activity.

引言
淋巴管参与组织稳态维持。尽管已知骨骼肌内淋巴管在萎缩、损伤等特定条件下会发生结构改变，但运动对肌内淋巴管的影响仍不明确。
方法
本研究旨在探究8周自愿转轮运动（VWR）是否会引发淋巴管与毛细血管的组织学改变，以及这些反应是否与年龄及肌纤维类型相关。将3月龄年轻雄性C57BL/6小鼠与18月龄老年雄性C57BL/6小鼠分为久坐组与VWR组，采用免疫组织化学法与定量聚合酶链式反应对比目鱼肌（SOL，慢肌）与跖肌（PLAN，快肌）进行检测分析。
结果
在年轻小鼠中，VWR可增加I型肌纤维数量，并显著提升比目鱼肌内淋巴管与毛细血管的密度，同时上调血管内皮生长因子C（VEGF-C）与血管内皮生长因子D（VEGF-D）的表达水平。而老年小鼠以及两个年龄组小鼠的跖肌均未出现此类变化。
讨论
尽管老年小鼠的I型肌纤维数量同样出现上升，但未出现相应的血管重塑现象，这表明衰老会降低机体对运动诱导的血管生成与淋巴管生成信号的响应能力。综上，本研究结果显示，VWR可促进年轻小鼠慢肌内的淋巴管生成与血管生成，这可能是为适应氧气需求增加而产生的适应性反应。骨骼肌内运动诱导的血管与淋巴管重塑显著受年龄与肌纤维类型影响，这凸显了老年肌肉的适应能力下降，该现象可能会对通过体育运动促进血管健康的相关策略产生影响。