Bilic Z, Gojkovic S, Kalogjera L, Krezic I, Malekinusic D, Knezevic M, Sever M, Lojo N, Kokot A, Kasnik K, Kralj T, Vukojevic J, Siroglavic M, Peklic M, Drmic D, Milavic M, Sikiric S, Skorak I, Brizic I, Hriberski K, Kubat M, Vladic J, Boban Blagaic A, Tvrdeic A, Skrtic A, Seiwerth S, Sikiric P
Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia.
Department of Anatomy and Neuroscience, Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia.
J Physiol Pharmacol. 2021 Dec;72(6). doi: 10.26402/jpp.2021.6.11. Epub 2022 Apr 24.
Surgically perforated stomach (since direct injury in rats until persisting defect and huge adhesions (day 1, day 7)) fairly represent an unresolved cytoprotection issue, and thereby, we focused resolving of the immediate triad, particular vascular failure (vessels 'disappear'/empty), prolonged bleeding, debilitated defect large widening. Agents (mg/kg) or saline (controls) were given at 1 min post-injury as an abdominal bath (10 ml/rat throughout 2 min). Within 1 - 15 min post-injury period, with cytoprotective BPC 157 (0.01 μg), the rapidly restored vessels 'run' (vessels filled/reappeared) toward the perforated defect, and there is less bleeding, and defect contraction; advanced perforated lesion healing (day 1) to complete healing (day 7), and less adhesions. With pantoprazole (10 mg), early (vessels (worsening), bleeding (prolongation), defect (attenuated widening)) effect means eventual lesions and adhesions severity as in controls. Ranitidine (10 mg) early effect (vessels (improvement), bleeding (less bleeding), defect (eliminated widening, defect not changed)) means final lesions attenuation, but not complete healing, less adhesions. L-NAME (5 mg) early (vessels worsening, less bleeding, attenuated defect widening) and final (lesions aggravation, more adhesions) effect, versus L-arginine (100 mg) early (vessels improvement, more bleeding, attenuated defect widening) and final (lesions attenuation, less adhesions) effect, combined few simultaneously occurring nitric oxide (NO)-system distinct processes. Finally, in the stomach tissue surrounding defect, increased malondialdehyde (MDA)- and decreased NO-values, BPC 157 reversed to the normal healthy values, and mRNA expression studies (Cox2, VEGFa, Nos1, Nos 2, Nos3, Nkap (NF-kappa-B-activating protein gene)), done at that very early post-perforation-time, indicate a way how BPC 157 may act beneficially in the perforated stomach lesion throughout NO- and prostaglandinds-system.
手术造成的胃穿孔（从大鼠直接损伤直至持续存在缺损和大量粘连（第1天、第7天））相当程度上代表了一个尚未解决的细胞保护问题，因此，我们专注于解决直接出现的三联征，尤其是血管衰竭（血管“消失”/排空）、持续性出血、衰弱的缺损大幅扩大。在损伤后1分钟给予药物（毫克/千克）或生理盐水（对照组）进行腹腔灌注（整个2分钟内每只大鼠10毫升）。在损伤后1至15分钟内，使用具有细胞保护作用的BPC 157（0.01微克）时，血管迅速恢复“运行”（血管充盈/重新出现），朝向穿孔缺损处，出血减少，缺损收缩；穿孔性病变在第1天进展至第7天完全愈合，粘连减少。使用泮托拉唑（10毫克）时，早期（血管（恶化）、出血（延长）、缺损（扩大减弱））效应意味着最终病变和粘连严重程度与对照组相同。雷尼替丁（10毫克）的早期效应（血管（改善）、出血（出血减少）、缺损（扩大消除、缺损未改变））意味着最终病变减轻，但未完全愈合，粘连减少。L - 精氨酸甲酯（L - NAME，5毫克）的早期（血管恶化、出血减少、缺损扩大减弱）和最终（病变加重、粘连增多）效应，与L - 精氨酸（100毫克）的早期（血管改善、出血增多、缺损扩大减弱）和最终（病变减轻、粘连减少）效应，共同体现了一氧化氮（NO）系统中几个同时发生的不同过程。最后，在缺损周围的胃组织中，丙二醛（MDA）值升高而NO值降低，BPC 157使其恢复到正常健康值，并且在穿孔后极早期进行的mRNA表达研究（Cox2、VEGFa、Nos1、Nos2、Nos3、Nkap（NF - κB激活蛋白基因））表明了BPC 157在穿孔性胃病变中可能通过NO和前列腺素系统发挥有益作用的方式。
