Androgenic-anabolic steroids associated with mechanical loading inhibit matrix metallopeptidase activity and affect the remodeling of the Achilles tendon in rats
Androgenic-anabolic steroids associated with mechanical loading inhibit matrix metallopeptidase activity and affect the remodeling of the Achilles tendon in rats
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DOI：
10.1177/0363546506286867
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发表时间：
2006-08-01
影响因子：
4.8
通讯作者：
Selistre-de-Araujo, Heloisa S.
中科院分区：
文献类型：
--
作者：
Marqueti, Rita C.;Parizotto, Nivaldo A.;Selistre-de-Araujo, Heloisa S.
背景资料：在几种情况下，不加选择地使用合成代谢雄激素类固醇已被证明会诱导跟腱的病理变化。目的：研究用合成代谢雄激素类固醇联合运动计划治疗的大鼠的肌腱重塑。研究设计：对照实验室研究。方法：Wistar大鼠分组如下：久坐（组I）、仅注射合成代谢雄激素类固醇（组II）、仅训练（组III）以及训练并注射合成代谢雄激素类固醇（组IV）。训练组在水中进行跳跃：4个系列，每个系列10次跳跃，过载为动物体重的50%至70%，系列之间休息30秒，持续6周。皮下注射合成代谢雄激素类固醇（5 mg/kg）。活性的基质金属肽酶，肌腱重塑的标志物，在组织提取物中进行了分析，明胶-十二烷基硫酸钠-聚丙烯酰胺凝胶electrophoresis.Results：肌腱的形态学分析表明，在第二组，最外层，覆盖肌腱较厚的胶原纤维聚集，这表明胶原合成增加。在组IV中，观察到肌腱中的炎性浸润和纤维化以及血清皮质酮水平的显著增加。这种训练方案上调基质金属肽酶活性，而蛋白同化雄激素治疗强烈抑制这种活性。分子量约为62和58 kDa的溶解条带的出现表明基质金属肽酶-2活化。结论：蛋白同化-雄激素类固醇治疗可通过下调基质金属肽酶活性来损害运动动物肌腱的组织重塑，从而增加肌腱损伤的可能性。由于AAS的滥用是如此普遍，更好地了解这些药物引起的病理效应可能有助于开发新的AAS诱导的病变治疗形式。
Background: The indiscriminate use of anabolic-androgenic steroids has been shown to induce pathologic changes in the Achilles tendon in several situations.Purpose: To study tendon remodeling in rats treated with anabolic-androgenic steroids combined with an exercise program.Study Design: Controlled laboratory study.Methods: Wistar rats were grouped as follows: sedentary (group I), injected with anabolic-androgenic steroids only (group II), trained only (group III), and trained and injected with anabolic-androgenic steroids (group IV). The trained groups performed jumps in water: 4 series of 10 jumps each, with an overload of 50% to 70% of the animal's body weight and a 30-second rest interval between series, for 6 weeks. Anabolic-androgenic steroids (5 mg/kg) were injected subcutaneously. Activity of matrix metallopeptidases, a marker for tendon remodeling, was analyzed in tissue extracts by zymography on gelatin-sodium dodecyl sulfate-polyacrylamide gel electrophoresis.Results: Morphological analyses of tendons showed that in group II, the most external layer that covers the tendon was thicker with aggregation of the collagen fibers, suggesting an increase in collagen synthesis. In group IV, an inflammatory infiltrate and fibrosis in tendons as well as a pronounced increase of the serum corticosterone level were observed. This training protocol upregulated matrix metallopeptidase activity, whereas anabolic-androgenic steroid treatment strongly inhibited this activity. The appearance of lytic bands with molecular masses of approximately 62 and 58 kDa suggests the activation of matrix metallopeptidase-2.Conclusion: Anabolic-androgenic steroid treatment can impair tissue remodeling in the tendons of animals undergoing physical exercise by downregulating matrix metal lopepticlase activity, thus increasing the potential for tendon injury.Clinical Relevance: Since the AAS abuse is so widespread, a better comprehension of the pathological effects induced by these drugs may be helpful for the development of new forms of therapy of AAS-induced lesions.