Modulating Glucose Metabolism and Lactate Synthesis in Injured Mouse Tendons: Treatment With Dichloroacetate, a Lactate Synthesis Inhibitor, Improves Tendon Healing.
Modulating Glucose Metabolism and Lactate Synthesis in Injured Mouse Tendons: Treatment With Dichloroacetate, a Lactate Synthesis Inhibitor, Improves Tendon Healing.
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调节受伤小鼠肌腱的葡萄糖代谢和乳酸合成：用乳酸合成抑制剂二氯乙酸治疗可改善肌腱愈合。
DOI：
10.1177/0363546518778789
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Enomoto-Iwamoto M
中科院分区：
文献类型：
--
作者：
Zhang K;Hast MW;Izumi S;Usami Y;Shetye S;Akabudike N;Philp NJ;Iwamoto M;Nissim I;Soslowsky LJ;Enomoto-Iwamoto M
肌腱损伤是运动员的常见问题。肌腱断裂的机械结构和功能的完全恢复是具有挑战性的。研究表明，糖酵解和乳酸生成的上调发生在伤口、炎症部位和癌性肿瘤中，这些代谢变化也控制着干细胞和祖细胞的生长和分化。类似的代谢变化在人类愈合肌腱中也有报道。此外，IL-1β处理后，损伤肌腱分离的祖细胞乳酸生成增加。人们认为，代谢变化在损伤后肌腱愈合中起作用。葡萄糖代谢在肌腱损伤和愈合过程中发生改变，调节这种改变的代谢可促进肌腱修复。对照实验室研究。作者采用C57BL/6J雌性小鼠跟腱全切口肌腱损伤模型，术后1周和4周采用[U-13C]葡萄糖和代谢组学分析研究损伤肌腱的糖代谢变化。他们还在同一小鼠模型中检测了二氯乙酸（DCA，一种间接乳酸合成抑制剂）治疗对术后4周损伤肌腱结构和力学性能恢复的影响。损伤手术后肌腱的葡萄糖代谢发生了显著变化。损伤后1周，代谢物和中间体的13C富集、糖酵解通量和乳酸合成以及三羧酸循环活性急剧增加。损伤后4周也发现糖酵解和乳酸生成增加。与车辆处理的损伤肌腱相比，dca处理的损伤肌腱的横截面积减小，模量、最大应力和最大力值更高。DCA组胶原纤维的排列也有所改善。此外，DCA治疗减少了损伤肌腱的粘液积聚和异位钙化。结果表明，损伤肌腱损伤后糖酵解和乳酸合成急剧增加，DCA抑制乳酸合成有利于肌腱愈合。损伤肌腱代谢的改变可能是肌腱修复的治疗靶点。
Tendon injuries are common problems among athletes. Complete recovery of the mechanical structure and function of ruptured tendons is challenging. It has been demonstrated that upregulation of glycolysis and lactate production occurs in wounds, inflammation sites, and cancerous tumors, and these metabolic changes also control growth and differentiation of stem and progenitor cells. Similar metabolic changes have been reported in human healing tendons. In addition, lactate production has increased in progenitors isolated from injured tendons after treatment with IL-1β. It is thought that the metabolic changes play a role in tendon healing after injury. Glucose metabolism is altered during tendon injury and healing, and modulation of this altered metabolism improves tendon repair. Controlled laboratory study. The authors used the tendon injury model involving a complete incision of Achilles tendon in C57BL/6J female mice and studied alterations of glucose metabolism in injured tendons with [U-13C]glucose and metabolomics analysis 1 and 4 weeks after surgery. They also examined the effects of dichloroacetate (DCA; an indirect lactate synthesis inhibitor) treatment on the recovery of structure and mechanical properties of injured tendons 4 weeks after surgery in the same mouse model. Significant changes in glucose metabolism in tendons after injury surgery were detected. 13C enrichment of metabolites and intermediates, flux through glycolysis, and lactate synthesis, as well as tricarboxylic acid cycle activity, were acutely increased 1 week after injury. Increased glycolysis and lactate generation were also found 4 weeks after injury. DCA-treated injured tendons showed decreased cross-sectional area and higher values of modulus, maximum stress, and maximum force when compared with vehicle-treated injured tendons. Improved alignment of the collagen fibers was also observed in the DCA group. Furthermore, DCA treatment reduced mucoid accumulation and ectopic calcification in injured tendons. The findings indicate that injured tendons acutely increased glycolysis and lactate synthesis after injury and that the inhibition of lactate synthesis by DCA is beneficial for tendon healing. Changing metabolism in injured tendons may be a therapeutic target for tendon repair.
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影响因子：
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