Krivic Andrija, Anic Tomislav, Seiwerth Sven, Huljev Dubravko, Sikiric Predrag
Laboratory for Experimental Surgery, Department of Pharmacology, University of Zagreb Medical School, Salata 11, Zagreb 10000, Croatia.
J Orthop Res. 2006 May;24(5):982-9. doi: 10.1002/jor.20096.
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.
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。