Staresinic Mario, Petrovic Igor, Novinscak Tomislav, Jukic Ivana, Pevec Damira, Suknaic Slaven, Kokic Neven, Batelja Lovorka, Brcic Luka, Boban-Blagaic Alenka, Zoric Zdenka, Ivanovic Domagoj, Ajduk Marko, Sebecic Bozidar, Patrlj Leonardo, Sosa Tomislav, Buljat Gojko, Anic Tomislav, Seiwerth Sven, Sikiric Predrag
Department of Pharmacology, School of Medicine, University of Zagreb, Salata 11, P.O.B. 916, 10000 Zagreb, Croatia.
J Orthop Res. 2006 May;24(5):1109-17. doi: 10.1002/jor.20089.
We report complete transection of major muscle and the systemic peptide treatment that induces healing of quadriceps muscle promptly and then maintains the healing with functional restoration. Initially, stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419, PL-10, PLD-116, PL 14736 Pliva, Croatia; in trials for inflammatory bowel disease; wound treatment; no toxicity reported; effective alone without carrier) also superiorly accelerates the healing of transected Achilles tendon. Regularly, quadriceps muscle completely transected transversely 1.0 cm proximal to patella presents a definitive defect that cannot be compensated in rat. BPC 157 (10 microg, 10 ng, 10 pg/kg) is given intraperitoneally, once daily; the first application 30 min posttransection, the final 24 h before sacrifice. It consistently improves muscle healing throughout the whole 72-day period. Improved are: (i) biomechanic (load of failure increased); (ii) function (walking recovery and extensor postural thrust/motor function index returned toward normal healthy values); (iii) microscopy/immunochemistry [i.e., mostly muscle fibers connect muscle segments; absent gap; significant desmin positivity for ongoing regeneration of muscle; larger myofibril diameters on both sides, distal and proximal (normal healthy rat-values reached)]; (iv) macroscopic presentation (stumps connected; subsequently, atrophy markedly attenuated; finally, presentation close to normal noninjured muscle, no postsurgery leg contracture). Thus, posttransection healing-consistently improved-may suggest this peptide therapeutic application in muscle disorders.
我们报告了主要肌肉的完全横断以及全身肽治疗，该治疗能迅速诱导股四头肌愈合，随后维持愈合并恢复功能。最初，稳定的胃十五肽BPC 157（GEPPPGKPADDAGLV，分子量1419，PL - 10，PLD - 116，克罗地亚普利瓦公司的PL 14736；用于炎症性肠病试验；伤口治疗；未报告毒性；无需载体单独有效）也能显著加速横断的跟腱愈合。通常，在髌骨近端1.0厘米处完全横向横断的股四头肌在大鼠中会出现无法代偿的明确缺损。BPC 157（10微克、10纳克、10皮克/千克）腹腔内注射，每日一次；在横断后30分钟首次给药，在处死前最后24小时给药。在整个72天期间，它持续改善肌肉愈合情况。改善的方面包括：（i）生物力学（破坏负荷增加）；（ii）功能（行走恢复以及伸肌姿势推力/运动功能指数恢复至正常健康值）；（iii）显微镜检查/免疫化学[即，大部分肌纤维连接肌肉段；无间隙；正在进行的肌肉再生有明显的结蛋白阳性；远端和近端两侧的肌原纤维直径更大（达到正常健康大鼠的值）]；（iv）宏观表现（残端连接；随后，萎缩明显减轻；最后，表现接近正常未受伤肌肉，术后腿部无挛缩）。因此，横断后持续改善的愈合情况可能表明这种肽在肌肉疾病治疗中的应用前景。
