Staresinic M, Sebecic B, Patrlj L, Jadrijevic S, Suknaic S, Perovic D, Aralica G, Zarkovic N, Borovic S, Srdjak M, Hajdarevic K, Kopljar M, Batelja L, Boban-Blagaic A, Turcic I, Anic T, Seiwerth S, Sikiric P
Department of Pharmacology, Medical Faculty, University of Zagreb, Salata 11, Post Box 916, 10000 Zagreb, Croatia.
J Orthop Res. 2003 Nov;21(6):976-83. doi: 10.1016/S0736-0266(03)00110-4.
In studies intended to improve healing of transected Achilles tendon, effective was a stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419). Currently in clinical trials for inflammatory bowel disease (PLD-116, PL 14736, Pliva), it ameliorates internal and external wound healing. In rats, the right Achilles tendon transected (5 mm proximal to its calcaneal insertion) presents with a large tendon defect between cut ends. Agents (/kg b.w., i.p., once time daily) (BPC 157 (dissolved in saline, with no carrier addition) (10 microg, 10 ng or 10 pg) or saline (5.0 ml)), were firstly applied at 30 min after surgery, the last application at 24 h before autopsy. Achilles functional index (AFI) was assessed once time daily. Biomechanical, microscopical and macroscopical assessment was on day 1, 4, 7, 10 and 14. Controls generally have severely compromised healing. In comparison, pentadecapeptide BPC 157 fully improves recovery: (i) biomechanically, increased load of failure, load of failure per area and Young's modulus of elasticity; (ii) functionally, significantly higher AFI-values; (iii) microscopically, more mononuclears and less granulocytes, superior formation of fibroblasts, reticulin and collagen; (iv) macroscopically, smaller size and depth of tendon defect, and subsequently the reestablishment of full tendon integrity. Likewise, unlike TGF-beta, pentadecapeptide BPC 157, presenting with no effect on the growth of cultured cell of its own, consistently opposed 4-hydroxynonenal (HNE), a negative modulator of the growth. HNE-effect is opposed in both combinations: BPC 157+HNE (HNE growth inhibiting effect reversed into growth stimulation of cultured tendocytes) and HNE+BPC 157(abolished inhibiting activity of the aldehyde), both in the presence of serum and serum deprived conditions. In conclusion, these findings, particularly, Achilles tendon transection fully recovered in rats, peptide stability suitable delivery, usefully favor gastric pentadecapeptide BPC 157 in future Achilles tendon therapy.
在旨在促进切断的跟腱愈合的研究中，稳定的胃十五肽BPC 157（GEPPPGKPADDAGLV，分子量1419）显示出有效性。目前它正在进行炎症性肠病的临床试验（PLD - 116，PL 14736，普利瓦公司），能改善内外部伤口愈合。在大鼠中，右跟腱在其跟骨附着点近端5毫米处切断后，断端之间会出现较大的肌腱缺损。将药物（按体重/千克，腹腔注射，每日一次）（BPC 157（溶解于生理盐水中，未添加载体）（10微克、10纳克或10皮克）或生理盐水（5.0毫升））在手术后30分钟首次给药，最后一次给药在尸检前24小时。每天评估一次跟腱功能指数（AFI）。在第1、4、7、10和14天进行生物力学、显微镜和大体评估。对照组的愈合通常严重受损。相比之下，十五肽BPC 157能完全促进恢复：（i）生物力学方面，增加破坏负荷、单位面积破坏负荷和杨氏弹性模量；（ii）功能方面，AFI值显著更高；（iii）显微镜下，单核细胞增多，粒细胞减少，成纤维细胞、网状纤维和胶原蛋白形成更好；（iv）大体上，肌腱缺损的大小和深度更小，随后肌腱完全恢复完整性。同样，与转化生长因子 - β不同，胃十五肽BPC 157对其自身培养细胞的生长没有影响，始终拮抗4 - 羟基壬烯醛（HNE），一种生长的负调节剂。在血清存在和血清缺乏条件下，在两种组合中HNE的作用都被拮抗：BPC 157 + HNE（HNE对培养肌腱细胞的生长抑制作用逆转为生长刺激作用）和HNE + BPC 157（消除醛的抑制活性）。总之，这些发现，特别是大鼠跟腱切断后完全恢复、肽稳定性适合给药，有利于胃十五肽BPC 157在未来跟腱治疗中的应用。
