高强度间歇训练通过乳酸/GPR81/ERK信号通路促进小鼠大脑皮质血管生成OA
High-intensity interval training promotes angiogenesis in the cerebral cortex of mice through the lactate/GPR81/ERK signaling pathway
目的:探讨高强度间歇训练(HIIT)是否通过乳酸/乳酸受体G蛋白偶联受体81(GPR81)/ERK通路促进小鼠大脑皮质血管生成.方法:将9周龄C57BL/6J小鼠随机分为正常对照组和HIIT组,HIIT组进行为期6周的HIIT.将小鼠脑血管内皮细胞系(bEnd.3)分为对照组、乳酸组、乳酸+ERK抑制剂组、GPR81激动剂组和GPR81激动剂+ERK抑制剂组.通过免疫荧光染色观察小鼠大脑皮质微血管密度和长度,免疫印迹法检测大脑皮质胶原蛋白Ⅳ、GPR81和ERK及p-ERK蛋白的表达;细胞划痕实验、CCK-8法和Matrigel成管实验分别检测bEnd.3细胞迁移、增殖和小管形成能力.结果:单次HIIT显著升高小鼠的血乳酸水平;6周HIIT可增加小鼠大脑皮质微血管密度和长度,上调胶原蛋白Ⅳ、GPR81蛋白表达和ERK磷酸化水平.乳酸干预和GPR81的激活均可促进bEnd.3细胞的增殖、迁移和成管能力;抑制ERK可减弱乳酸和GPR81激动剂对细胞增殖、迁移和成管能力的促进作用.结论:HIIT可通过乳酸/GPR81/ERK途径促进小鼠大脑皮质血管生成.
Objective:To investigate whether high-intensity interval training(HIIT)promotes cerebral cortical angiogenesis in mice through the lactate/G-protein-coupled receptor 81(GPR81)/extracellular signal-regulated kinase(ERK)signaling pathway.Methods:Nine-week-old C57BL/6J mice were randomly assigned to a control group or a HIIT group subjected to a 6-week training regimen.Mouse cerebral vascular endothelial cells(bEnd.3)were divided to control group,lactate group,lactate+ERK inhibitor group,GPR81 agonist group and GPR81 agonist+ERK inhibitor group.Cortical microvascular density and length were evaluated by immunofluorescence staining.Protein expression of collagen Ⅳ,GPR81,total ERK,and phosphorylated ERK(p-ERK)was analyzed by Western blotting.Cell migration,proliferation,and tube-forming ability were assessed by wound healing,CCK-8,and Matrigel tube formation assays,respectively.Results:A single bout of HIIT significantly elevated blood lactate levels.After the 6-week intervention,HIIT enhanced cortical angiogenesis,as indicated by increased microvascular density and length,and upregulation of collagen Ⅳ,GPR81,and p-ERK expression.In vitro,both lactate and GPR81 activation enhanced bEnd.3 cell proliferation,migration,and tube formation.Notably,ERK inhibition attenuated the lactate-and GPR81 agonist-induced enhancement of these cellular functions.Conclusion:HIIT induces angiogenesis in the mouse cerebral cortex through the lactate/GPR81/ERK signaling pathway.
童玥;卞学鹏;邓梦婷;商庆慧;刘俊;祝露桃;娄淑杰
台州学院医学院康复医学系,台州 318000||上海体育大学运动健康学院,上海 200438上海杉达学院国际医学技术学院,上海 201209||上海体育大学运动健康学院,上海 200438上海体育大学运动健康学院,上海 200438上海体育大学运动健康学院,上海 200438上海体育大学运动健康学院,上海 200438上海体育大学运动健康学院,上海 200438上海体育大学运动健康学院,上海 200438
医药卫生
高强度间歇训练大脑皮质血管生成乳酸G蛋白偶联受体81细胞外调节蛋白激酶
high-intensity interval trainingcerebral cortexangiogenesislactateG-protein-coupled receptor 81extracellular signal-regulated protein kinase
《解剖学杂志》 2026 (4)
326-333,367,9
国家自然科学基金(31971098)上海市人类运动能力开发与保障重点实验室(上海体育大学)资助项目(11DZ2261100)
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