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大鼠跟腱断裂与稳定的胃十五肽BPC 157:促进腱骨愈合并对抗皮质类固醇的加重作用。

Achilles detachment in rat and stable gastric pentadecapeptide BPC 157: Promoted tendon-to-bone healing and opposed corticosteroid aggravation.

作者信息

Krivic Andrija, Anic Tomislav, Seiwerth Sven, Huljev Dubravko, Sikiric Predrag

机构信息

Laboratory for Experimental Surgery, Department of Pharmacology, University of Zagreb Medical School, Salata 11, Zagreb 10000, Croatia.

出版信息

J Orthop Res. 2006 May;24(5):982-9. doi: 10.1002/jor.20096.

Abstract

Stable gastric pentadecapeptide BPC 157 (BPC 157, as an antiulcer agent in clinical trials for inflammatory bowel disease; PLD-116, PL 14736, Pliva, no toxicity reported) alone (without carrier) ameliorates healing of tendon and bone, respectively, as well as other tissues. Thereby, we focus on Achilles tendon-to-bone healing: tendon to bone could not be healed spontaneously, but it was recovered by this peptide. After the rat's Achilles tendon was sharply transected from calcaneal bone, agents [BPC 157 (10 microg, 10 ng, 10 pg), 6alpha-methylprednisolone (1 mg), 0.9% NaCl (5 mL)] were given alone or in combination [/kg body weight (b.w.) intraperitoneally, once time daily, first 30-min after surgery, last 24 h before analysis]. Tested at days 1, 4, 7, 10, 14, and 21 after Achilles detachment, BPC 157 improves healing functionally [Achilles functional index (AFI) values substantially increased], biomechanically (load to failure, stiffness, and Young elasticity modulus significantly increased), macro/microscopically, immunohistochemistry (better organization of collagen fibers, and advanced vascular appearance, more collagen type I). 6alpha-Methylprednisolone consistently aggravates the healing, while BPC 157 substantially reduces 6alpha-methylprednisolone healing aggravation. Thus, direct tendon-to-bone healing using stabile nontoxic peptide BPC 157 without a carrier might successfully exchange the present reconstructive surgical methods.

摘要

稳定的胃十五肽BPC 157(BPC 157,作为一种在炎症性肠病临床试验中的抗溃疡药物;PLD - 116,PL 14736,普利瓦,未报告有毒性)单独使用(无载体)可分别改善肌腱和骨骼以及其他组织的愈合。因此,我们专注于跟腱到骨的愈合:肌腱到骨无法自发愈合,但这种肽可使其恢复。在大鼠的跟腱从跟骨处锐性横断后,单独或联合给予药物[BPC 157(10微克、10纳克、10皮克)、6α - 甲基泼尼松龙(1毫克)、0.9%氯化钠(5毫升)][/千克体重腹腔内注射,每天一次,在手术后的前30分钟,在分析前的最后24小时]。在跟腱离断后的第1、4、7、10、14和21天进行测试,BPC 157在功能上改善愈合[跟腱功能指数(AFI)值大幅增加],在生物力学上(破坏载荷、刚度和杨氏弹性模量显著增加),在宏观/微观上,在免疫组织化学上(胶原纤维组织更好,血管外观更发达,I型胶原更多)。6α - 甲基泼尼松龙持续加剧愈合不良,而BPC 157则显著减轻6α - 甲基泼尼松龙对愈合的加剧作用。因此,使用无载体的稳定无毒肽BPC 157直接进行肌腱到骨的愈合可能成功替代目前的重建手术方法。

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