大鼠肠道粘连及用稳定的胃十五肽BPC 157、L-精氨酸甲酯（L-NAME）和L-精氨酸进行治疗
Bowel adhesion and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine in rats.
作者信息
Cesar Lidija Berkopic, Gojkovic Slaven, Krezic Ivan, Malekinusic Dominik, Zizek Helena, Vuletic Lovorka Batelja, Petrovic Andreja, Pavlov Katarina Horvat, Drmic Domagoj, Kokot Antonio, Vlainic Josipa, Seiwerth Sven, Sikiric Predrag
机构信息
Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb 10 000, Croatia.
Department of Pathology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia.
出版信息
World J Gastrointest Pharmacol Ther. 2020 Nov 8;11(5):93-109. doi: 10.4292/wjgpt.v11.i5.93.
BACKGROUND
After parietal peritoneum excision with an underlying superficial layer of muscle tissue in rats, there is failed vasculature, and finally, increased adhesion formation. We hypothesized that unlike nitric oxide (NO)-agents, L-NAME and/or L-arginine, the application of the stable gastric pentadecapeptide BPC 157 with its most recent vascular effects ("vascular recruitment") means attenuated bowel adhesion formation and NO- and malondialdehyde (MDA)-tissue values.
AIM
To focused on the bowel adhesion and the therapy with the BPC 157, its most and application of NO-agents.
METHODS
Along with defect creation, medication was (1) during surgery, once, at 1 min after defect creation as an abdominal bath (1 mL/rat), BPC 157 (10 µg/kg, 10 ng/kg, 1 mL/rat), an equivolume of saline, L-NAME (5 mg/kg), L-arginine (200 mg/kg) alone and/or combined. Alternatively, medication was (2) intraperitoneally once daily, first application at 30 min after surgery, last application 24 h before assessment at d 7 or d 14. As a postponed therapy to pre-existing adhesion (3), BPC 157 (10 µg/kg, 10 ng/kg intraperitoneally, 1 mL/rat) was given once daily since d 7.
RESULTS
The recovery effect of the BPC 157 regimens goes with the presence of abundant vascular vessels in and near the defect, which occurs rapidly. Lastly, also applied as post-treatment, BPC 157 creates attenuated adhesions, minimal or no adhesion. Contrarily, NO-agents have diverse initial and final effects: The initial weakening of blood vessel disappearance and finally, severe worsening of adhesions (L-NAME) the initial weakening of blood vessel disappearance and finally, attenuation of adhesions formation (L-arginine), which counteract each other response given together. Importantly, BPC 157 maintains its beneficial effect also when given with NO-agents (L-NAME + BC 157; L-arginine + BPC 157; L-NAME + L-arginine + BPC 157). Finally, with respect to the increased NO- and MDA- values-adhesion tissue formation relation, unlike diverse effect of the NO-agents, the BPC 157 application effect regularly combines decrease on the increased NO- and MDA- values and the beneficial outcome (less adhesion formation).
CONCLUSION
BPC 157 therapy can be suited for the realization of the peritoneal defect healing with minimal or no adhesion formation.
背景
在大鼠切除壁腹膜及其下方浅层肌肉组织后，会出现血管系统功能障碍，最终导致粘连形成增加。我们推测，与一氧化氮（NO）制剂L - 精氨酸甲酯（L - NAME）和/或L - 精氨酸不同，应用具有最新血管效应（“血管募集”）的稳定胃十五肽BPC 157可减少肠粘连形成以及NO和丙二醛（MDA）组织值。
目的
重点研究肠粘连以及BPC 157的治疗方法、其最新研究情况和NO制剂的应用。
方法
在制造缺损的同时进行给药，（1）在手术期间，于制造缺损后1分钟作为腹腔灌洗（1 mL/只大鼠）一次性给予BPC 157（10 μg/kg、10 ng/kg、1 mL/只大鼠）、等体积的生理盐水、L - NAME（5 mg/kg）、L - 精氨酸（200 mg/kg）单独使用和/或联合使用。或者，（2）每天腹腔内给药一次，首次给药于手术后30分钟，最后一次给药于第7天或第14天评估前24小时。作为对已存在粘连的延迟治疗（3），自第7天起每天腹腔内给予BPC 157（10 μg/kg、10 ng/kg，1 mL/只大鼠）一次。
结果
BPC 157治疗方案的恢复效果与缺损处及附近存在丰富血管有关，且这种情况迅速出现。最后，即使作为后期治疗应用，BPC 157也能减少粘连，形成极少或无粘连。相反，NO制剂具有不同的初始和最终效果：L - NAME使血管消失的初始减弱，最终粘连严重恶化；L - 精氨酸使血管消失的初始减弱，最终粘连形成减少，两者联合应用时相互抵消。重要的是，BPC 157与NO制剂（L - NAME + BC 157；L - 精氨酸 + BPC 157；L - NAME + L - 精氨酸 + BPC 157）联合使用时也能维持其有益效果。最后，关于NO和MDA值增加与粘连组织形成的关系，与NO制剂的不同效果不同，应用BPC 157的效果通常是使增加的NO和MDA值降低，并产生有益结果（粘连形成减少）。
结论
BPC 157治疗可适用于实现腹膜缺损愈合，且粘连形成极少或无粘连。
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