中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (3): 482-487.doi: 10.4103/1673-5374.320969

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

十五肽BPC 157与中枢神经系统

  

  • 出版日期:2022-03-15 发布日期:2021-10-14

Pentadecapeptide BPC 157 and the central nervous system

Jakša Vukojević1, *, Marija Milavić2, Darko Perović1, Spomenko Ilić1, Andrea Zemba Čilić3, Nataša Đuran4, Sanja Štrbe3, Zoran Zoričić5, Igor Filipčić6, Petrana Brečić4, Sven Seiverth2, Predrag Sikirić1#br#   

  1. 1Department of Pharmacology, Medical School, University of Zagreb, Zagreb, Croatia; 2Department of Pathology, Medical School, University of Zagreb, Zagreb, Croatia; 3University Clinical Hospital Center “Zagreb”, Zagreb, Croatia; 4University Psychiatric Hospital “Vrapče”, Zagreb, Croatia; 5University Clinical Hospital Center “Sestre Milosrdnice”, Zagreb, Croatia; 6Psychiatric Hospital “Sveti Ivan”, Zagreb, Croatia
  • Online:2022-03-15 Published:2021-10-14
  • Contact: Jakša Vukojević, MD, PhD, jaksa.vukojevic@bolnica-vrapce.hr.

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摘要： Neural Regen Res： 胃十五肽BPC 157治疗作用：无论直接或间接均在肠-脑轴内
稳定的胃十五肽BPC 157的多效性有益作用已在多个器官系统中报道。BPC 157是天然的胃十五肽，无毒且具有深层的细胞保护活性，已用于溃疡性结肠炎和多发性硬化试验。在人的胃液中，BPC 157可以稳定超过24小时，因此它具有良好的口服生物利用度，并且在整个胃肠道中具有有益作用。稳定的BPC 157被认为是Robert细胞保护的介体，可维持胃肠道黏膜的完整性。BPC 157对Robert细胞保护作用以及抵抗有害物质与细胞直接接触所引起的病变的能力代表肠道与脑轴之间的外围连接。最近研究表明BPC 157对卒中后的大鼠具有直接的治疗作用（即抵消海马缺血/再灌注引起的损伤）。与未经治疗的大鼠（未激活Mapk1）相比，BPC 157处理导致Egr1，Akt1，Kras，Src，Foxo，Srf，Vegfr2，Nos3和Nos1的上调以及Nos2和Nfkb的下调。明显的Egr1和Vegfr2上调表明BPC 157具有血管化特性，这种机制可能是其调节缺血/再灌注损伤的能力的基础。最有趣的发现是与对照动物相比，Nos3的强烈上调，Nos1的轻微上调和Nos2的抑制。这些作用可能为卒中提供一种新颖的治疗方案。
来自克罗地亚萨格勒布大学医学院的Jakša Vukojević团队认为首先，BPC 157可改变再灌注模型大鼠持续性脑神经元损伤以及记忆、运动和协调障碍。这种作用支持BPC 157治疗大鼠海马组织中出现的特定基因表达。其次，有L-NG-硝基精氨酸甲酯和氟哌啶醇诱导的催化反应，以及BPC157对抗的“阳性样”精神分裂症大鼠急慢性模型，解决了一氧化氮系统与安非他明和阿扑吗啡（多巴胺制剂应用）的复杂关系，MK-801（N-甲基-d-天冬氨酸受体的非竞争性拮抗剂）和慢性甲基苯丙胺给药（诱导敏感性）。第三，BPC157可促进大鼠脊髓压迫后的功能恢复。需要注意的是无论BPC157发挥的是直接还是间接作用都必须在肠道与脑轴内起作用。
文章在《中国神经再生研究（英文版）》杂志2022年 3月 3 期发表。


https://orcid.org/0000-0003-4215-6743 (Jakša Vukojević) 

Abstract: We reviewed the pleiotropic beneficial effects of the stable gastric pentadecapeptide BPC 157, three very recent demonstrations that may be essential in the gut-brain and brain-gut axis operation, and therapy application in the central nervous system disorders, in particular. Firstly, given in the reperfusion, BPC 157 counteracted bilateral clamping of the common carotid arteries-induced stroke, sustained brain neuronal damages were resolved in rats as well as disturbed memory, locomotion, and coordination. This therapy effect supports particular gene expression in hippocampal tissues that appeared in BPC 157-treated rats. Secondly, there are L-NG-nitro arginine methyl ester (L-NAME)- and haloperidol-induced catalepsy as well as the rat acute and chronic models of ‘positive-like’ schizophrenia symptoms, that BPC 157 counteracted, and resolved the complex relationship of the nitric oxide-system with amphetamine and apomorphine (dopamine agents application), MK-801 (non-competitive antagonist of the N-methyl-D-aspartate receptor) and chronic methamphetamine administration (to induce sensitivity). Thirdly, after rat spinal cord compression, there were advanced healing and functional recovery (counteracted tail paralysis).  Likewise, in BPC 157 therapy, there is specific support for each of these topics: counteracted encephalopathies; alleviated vascular occlusion disturbances (stroke); counteracted dopamine disturbances (dopamine receptors blockade, receptors super sensitivity development, or receptor activation,  over-release, nigrostriatal damage, vesicles depletion), and  nitric oxide-system disturbances (“L-NAME non-responsive, L-arginine responsive,” and “L-NAME responsive, L-arginine responsive”) (schizophrenia therapy); inflammation reduction, nerve recovery in addition to alleviated hemostasis and vessels function after compression (spinal cord injury therapy). Thus, these disturbances may be all resolved within the same agent’s beneficial activity, i.e., the stable gastric pentadecapeptide BPC 157.

Key words: BPC 157, central nervous system, cytoprotection, injury, nitric oxide system, peptide, regeneration