Expressional changes in growth and inflammatory mediators during Achilles tendon repair in diabetic rats: new insights into a possible basis for compromised healing
Expressional changes in growth and inflammatory mediators during Achilles tendon repair in diabetic rats: new insights into a possible basis for compromised healing
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DOI：
10.1007/s00441-014-1871-3
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发表时间：
2014-07-01
影响因子：
3.6
通讯作者：
Ackermann, Paul W.
中科院分区：
文献类型：
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作者：
Ahmed, Aisha S.;Li, Jian;Ackermann, Paul W.
在久坐不动的生活方式和2型糖尿病等疾病中，通常观察到的生长和炎症介质的失调可能会导致组织稳态和愈合的缺陷。本研究旨在评估生长和炎症介质在2型糖尿病大鼠完整和愈合跟腱中的表达变化。该研究使用了11只雄性糖尿病大鼠Goto-Kakizaki(GK)和10只年龄和性别匹配的Wistar对照组大鼠。所有动物的右侧跟腱均被切断，而左侧跟腱保持完好。损伤后2周，采用定量逆转录聚合酶链式反应技术检测完整和损伤肌腱中血管内皮生长因子、Tβ-4、转化生长因子-β1、胰岛素样生长因子-1、环氧合酶-2、诱导型一氧化氮合酶、缺氧诱导因子-1α和白介素1β的基因表达，并用免疫组织化学方法研究其蛋白分布。与Wistar对照组相比，糖尿病GK大鼠损伤肌腱中血管内皮生长因子和Tβ-4mRNA及相应蛋白的表达水平显著下调。与完整肌腱相比，糖尿病GK大鼠损伤肌腱中的转化生长因子-β1、胰岛素样生长因子-1和环氧合酶-2的RNA水平较高，而诱导型一氧化氮合酶的mRNA水平较低。在Wistar对照组中，损伤后2周愈合导致损伤肌腱中血管内皮生长因子和诱导型一氧化氮合酶基因表达显著下调，而转化生长因子-β1和缺氧诱导因子-1α基因表达水平与完整肌腱相比显著升高。因此，炎症和生长介质的失调发生在2型糖尿病损伤的肌腱中。我们的数据表明，Tβ-4和血管内皮生长因子的治疗调节代表了糖尿病手术、损伤或退行性肌腱疾病的一种新的再生途径。
Dysregulation of growth and inflammatory mediators might contribute to defective tissue homeostasis and healing, as commonly observed in sedentary lifestyles and in conditions such as diabetes mellitus type-2. The present study aims to assess expression changes in growth and inflammatory mediators in the intact and healing Achilles tendon of type-2 diabetic rats. The study utilized 11 male diabetic Goto-Kakizaki (GK) and 10 age- and sex-matched Wistar control rats. The right Achilles tendon was transected in all animals, whereas the left Achilles tendon remained intact. At 2 weeks post-injury, intact and injured tendons were assessed for gene expression for VEGF, T beta-4, TGF-beta 1, IGF-1, COX-2, iNOS, HIF-1 alpha, and IL-1 beta by quantitative reverse transcription plus the polymerase chain reaction, and their protein distribution was studied by immunolocalization. In injured tendons of diabetic GK rats, VEGF and T beta-4 mRNA and corresponding protein levels were significantly down-regulated compared with those of injured Wistar controls. Compared with intact tendons of diabetic GK rats, TGF-beta 1, IGF-1, and COX-2 RNA levels were higher, whereas iNOS mRNA levels were lower in injured tendons of diabetic GK rats. Within Wistar controls, healing at 2 weeks post-injury led to significantly down-regulated VEGF and iNOS mRNA levels in injured tendons, whereas TGF-beta 1 and HIF-1 alpha mRNA levels increased compared with intact tendons. Thus, dysregulation of inflammatory and growth mediators occurs in type-2 diabetes injured tendons. Our data suggest that therapeutic modulation of T beta-4 and VEGF represent a new regenerative approach in operated, injured, or degenerative tendon diseases in diabetes.