Sikiric P, Marovic A, Matoz W, Anic T, Buljat G, Mikus D, Stancic-Rokotov D, Separovic J, Seiwerth S, Grabarevic Z, Rucman R, Petek M, Ziger T, Sebecic B, Zoricic I, Turkovic B, Aralica G, Perovic D, Duplancic B, Lovric-Bencic M, Rotkvic I, Mise S, Jagic V, Hahn V
Department of Pharmacology, Medical Faculty University of Zagreb, Croatia.
J Physiol Paris. 1999 Dec;93(6):505-12. doi: 10.1016/s0928-4257(99)00119-9.
The effect of a stomach pentadecapeptide, BPC 157, on Parkinson's disease in mice was investigated, along with its salutary activity on stomach lesions induced by parkinsongenic agents. Parkinsongenic agents, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30.0 mg x kg(-1)b.w. i.p. once daily for 6d, and after 4d once 50.0 mg x kg(-1)b.w. i.p.) or reserpine (5.0 mg x kg(-1)b.w. i.p.) were applied i.p. BPC 157 (1.50 microg or 15.0 ng x kg(-1)b.w. i.p.) was applied 15 min before or alternatively 15 min after each MPTP administration. In reserpine studies, BPC 157 (10.0 microg or 10.0 ng x kg(-1)b.w. i.p.) was given either 15 min before reserpine or in the already established complete catalepsy 24 h thereafter. BPC 157 strongly improved the MPTP-impaired somatosensory orientation and reduced the MPTP-induced hyperactivity, and most importantly, MPTP-motor abnormalities (tremor, akinesia, catalepsy -otherwise very prominent in saline control), leading to almost complete abolition of otherwise regularly lethal course of MPTP treatment in controls. Likewise, in reserpine experiments, BPC 157 strongly prevented the development of otherwise very prominent catalepsy and when applied 24 h thereafter reversed the established catalepsy. In addition, a reduction of reserpine-hypothermy (BPC 157 pre-treatment) and reversal of further prominent temperature fall (BPC 157 post-treatment) have been consistently observed. Taking together these data, as the two most suitable animal models were consistently used and since the high effectiveness was demonstrated in pre- and post-treatment, microg and ng regimens, BPC 157 as an organoprotector should be further therapeutically investigated. Additionally, given in either regimen, pentadecapeptide BPC 157 strongly attenuated the stomach lesions in mice that otherwise consistently appeared in mice treated with the parkinsogenic neurotoxin MPTP.
研究了一种胃十五肽BPC 157对小鼠帕金森病的影响，以及它对帕金森病致病因子诱导的胃部损伤的有益作用。通过腹腔注射给予帕金森病致病因子，1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）（30.0 mg·kg⁻¹体重，每天腹腔注射一次，共6天，4天后再腹腔注射一次50.0 mg·kg⁻¹体重）或利血平（5.0 mg·kg⁻¹体重，腹腔注射）。在每次MPTP给药前15分钟或给药后15分钟腹腔注射BPC 157（1.50 μg或15.0 ng·kg⁻¹体重）。在利血平研究中，在利血平给药前15分钟或给药24小时后出现完全僵住症时腹腔注射BPC 157（10.0 μg或10.0 ng·kg⁻¹体重）。BPC 157显著改善了MPTP损伤的体感定向能力，降低了MPTP诱导的多动，最重要的是，改善了MPTP引起的运动异常（震颤、运动不能、僵住症——在生理盐水对照组中非常明显），几乎完全消除了对照组中MPTP治疗原本会导致的致命病程。同样，在利血平实验中，BPC 157强烈阻止了原本非常明显的僵住症的发展，并且在24小时后给药可逆转已形成的僵住症。此外，一直观察到利血平引起的体温过低有所降低（BPC 157预处理），以及进一步显著的体温下降得到逆转（BPC 157后处理）。综合这些数据，由于一直使用了两种最合适的动物模型，并且在预处理和后处理、微克和纳克给药方案中都证明了高效性，BPC 157作为一种器官保护剂应进一步进行治疗研究。此外，无论采用哪种给药方案，十五肽BPC 157都能强烈减轻小鼠的胃部损伤，而这种损伤在接受帕金森病致病神经毒素MPTP治疗的小鼠中一直会出现。
