Compromised Neurotrophic and Angiogenic Regenerative Capability during Tendon Healing in a Rat Model of Type-II Diabetes.
Compromised Neurotrophic and Angiogenic Regenerative Capability during Tendon Healing in a Rat Model of Type-II Diabetes.
复制标题
II型糖尿病大鼠模型中肌腱愈合期间的神经营养和血管生成能力受损。
DOI：
10.1371/journal.pone.0170748
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Ackermann PW
中科院分区：
文献类型：
--
作者：
Ahmed AS;Li J;Abdul AM;Ahmed M;Östenson CG;Salo PT;Hewitt C;Hart DA;Ackermann PW
代谢性疾病，如糖尿病II型（DM-II）可能会增加患疼痛性结缔组织疾病和肌腱断裂的风险。然而，糖尿病对结缔组织基质代谢和再生产生不利影响的病理机制仍需要更好的定义。我们的目的是研究DM-II对完整和愈合跟腱中神经和血管营养介质和受体表达变化的影响。在5只雄性DM-II Goto-Kakizaki（GK）和4只年龄匹配的Wistar对照大鼠中横断右侧跟腱。左侧跟腱完好无损。在损伤后2周，NGF，BDNF，TSP，和受体TrkA，TrkB和Nk 1基因表达的定量RT-PCR（qRT-PCR）和蛋白分布的免疫组织化学研究在完整和损伤的肌腱。通过qRT-PCR评价完整和损伤肌腱中肌腱相关标志物巩膜轴蛋白（SCX）和腱调节蛋白（TNMD）的表达。糖尿病GK大鼠损伤肌腱表现出显着下调Ngf和Tsp 1的mRNA和相应的蛋白水平，下调Trka基因的表达相比，受伤的Wistar对照组。DM-II GK大鼠的完整肌腱显示Ngf，Tsp 1和Trkb的mRNA水平降低，与相应的完整非糖尿病肌腱相比。正常和糖尿病GK大鼠损伤肌腱中观察到Scx和Tnmd基因表达上调相比，完整的Wistar对照。然而，这些分子并没有上调损伤的DM-II GK大鼠相比，其相应的控制。我们的研究结果表明，DM-II对神经和血管营养途径有不利影响，这种影响可能反映了糖尿病跟腱修复受损。因此，新的方法再生受伤，包括tendinopathic，和手术修复糖尿病肌腱可能包括神经营养途径，如神经生长因子及其受体的治疗分子调节。
Metabolic diseases such as diabetes mellitus type-II (DM-II) may increase the risk of suffering painful connective tissue disorders and tendon ruptures. The pathomechanisms, however, by which diabetes adversely affects connective tissue matrix metabolism and regeneration, still need better definition. Our aim was to study the effect of DM-II on expressional changes of neuro- and angiotrophic mediators and receptors in intact and healing Achilles tendon. The right Achilles tendon was transected in 5 male DM-II Goto-Kakizaki (GK) and 4 age-matched Wistar control rats. The left Achilles tendons were left intact. At week 2 post-injury, NGF, BDNF, TSP, and receptors TrkA, TrkB and Nk1 gene expression was studied by quantitative RT-PCR (qRT-PCR) and their protein distribution by immunohistochemistry in intact and injured tendons. The expression of tendon-related markers, Scleraxis (SCX) and Tenomodulin (TNMD), was evaluated by qRT-PCR in intact and injured tendons. Injured tendons of diabetic GK rats exhibited significantly down-regulated Ngf and Tsp1 mRNA and corresponding protein levels, and down-regulated Trka gene expression compared to injured Wistar controls. Intact tendons of DM-II GK rats displayed reduced mRNA levels for Ngf, Tsp1 and Trkb compared to corresponding intact non-diabetic tendons. Up-regulated Scx and Tnmd gene expression was observed in injured tendons of normal and diabetic GK rats compared to intact Wistar controls. However, these molecules were not up-regulated in injured DM-II GK rats compared to their corresponding controls. Our results suggest that DM-II has detrimental effects on neuro- and angiotrophic pathways, and such effects may reflect the compromised repair seen in diabetic Achilles tendon. Thus, novel approaches for regeneration of injured, including tendinopathic, and surgically repaired diabetic tendons may include therapeutic molecular modulation of neurotrophic pathways such as NGF and its receptors.