Type 2 diabetes impairs tendon repair after injury in a rat model
Type 2 diabetes impairs tendon repair after injury in a rat model
复制标题
DOI：
10.1152/japplphysiol.00767.2012
复制
发表时间：
2012-12-01
影响因子：
3.3
通讯作者：
Ackermann, Paul W.
中科院分区：
文献类型：
--
作者：
Ahmed, Aisha S.;Schizas, Nikos;Ackermann, Paul W.
Ahmed AS、Schizas N、Li J、Ahmed M、Ostenson CG、Salo P、Hewitt C、Hart DA、Ackermann PW。 2 型糖尿病会损害大鼠模型损伤后的肌腱修复。 J Appl Physiol 113: 1784-1791, 2012。首次发表于 2012 年 10 月 4 日； doi: 10.1152/japplphyol.00767.2012.-2 型糖尿病对天然结缔组织的特性产生不利影响。然而，糖尿病改变结缔组织代谢（尤其是肌腱）的潜在机制尚不清楚。本研究的目的是确定 2 型糖尿病对完整和愈合跟腱的机械、组织学和分子特性的影响。 11 只雄性糖尿病 Goto-Kakizaki (GK) 和 10 只年龄和性别匹配的 Wistar 对照大鼠的右侧跟腱被横断，而左侧跟腱则保持完整。受伤后 2 周，通过生物力学测试和组织学评估完整和受伤的肌腱。通过定量 RT-PCR 测量胶原蛋白 I 和 III、双糖链蛋白聚糖、多功能蛋白聚糖、MMP-13 和 MMP-3 的基因表达，并通过免疫组织化学研究它们的蛋白分布。完整的肌腱在各组之间仅表现出很小的差异。然而，在受伤的肌腱中，与 Wistar 对照大鼠相比，糖尿病 GK 的横向面积明显更小，硬度也更低。与 Wistar 对照相比，这与糖尿病 GK 受损肌腱中胶原纤维结构组织受损以及胶原蛋白 I 和 III 的表达减少相关。此外，与受伤的 Wistar 对照相比，受损的糖尿病 GK 肌腱中 MMP-3 基因表达下调。我们的结果表明，在糖尿病大鼠模型中，肌腱愈合受损主要是由于胶原蛋白和 MMP 表达的改变，反映出基质蛋白降解减少和组织重塑受损。此外，我们的数据表明，胶原蛋白或 MMP 的治疗性调节可能成为手术、受伤或糖尿病退行性肌腱疾病的新再生方法的目标。
Ahmed AS, Schizas N, Li J, Ahmed M, Ostenson CG, Salo P, Hewitt C, Hart DA, Ackermann PW. Type 2 diabetes impairs tendon repair after injury in a rat model. J Appl Physiol 113: 1784-1791, 2012. First published October 4, 2012; doi: 10.1152/japplphysiol.00767.2012.-Type 2 diabetes adversely affects the properties of native connective tissue. The underlying mechanisms, however, by which diabetes alters connective tissue metabolism, especially tendon, are poorly defined. The aim of this study was to determine the effect of type 2 diabetes on the mechanical, histological, and molecular properties of the intact and healing Achilles tendon. The right Achilles tendon was transected in 11 male diabetic Goto-Kakizaki (GK) and 10 age- and sex-matched Wistar control rats, while the left Achilles tendon was left intact. At 2 wk postinjury the intact and injured tendons were assessed by biomechanical testing and histology. The gene expression of collagen I and III, biglycan, versican, MMP-13, and MMP-3 was measured by quantitative RT-PCR, and their protein distribution was studied by immunohistochemistry. Intact tendons exhibited only small differences between the groups. In injured tendons, however, a significantly smaller transverse area and lower stiffness was found in diabetic GK compared with Wistar control rats. This correlated with impaired structural organization of collagen fibers and a reduced expression of collagen I and III in the injured tendons of the diabetic GK compared with Wistar control. Moreover, MMP-3 gene expression was down-regulated in the injured diabetic GK tendons compared with injured Wistar controls. Our results indicate that in a rat model of diabetes tendon healing is impaired mainly due to altered expression of collagen and MMPs reflecting decreased degradation of matrix proteins and impaired tissue remodeling. Further our data suggest that therapeutic modulation of collagens or MMPs might be targets for new regenerative approaches in operated, injured, or maybe also degenerative tendon diseases in diabetes.