Gojkovic Slaven, Krezic Ivan, Vrdoljak Borna, Malekinusic Dominik, Barisic Ivan, Petrovic Andreja, Horvat Pavlov Katarina, Kolovrat Marijan, Duzel Antonija, Knezevic Mario, Kasnik Kovac Katarina, Drmic Domagoj, Batelja Vuletic Lovorka, Kokot Antonio, Boban Blagaic Alenka, Seiwerth Sven, Sikiric Predrag
Departments of Pharmacology and Pathology, Medical Faculty University of Zagreb, Zagreb 10000, Croatia.
World J Gastrointest Pathophysiol. 2020 Mar 13;11(1):1-19. doi: 10.4291/wjgp.v11.i1.1.
Recently, as a possible therapy resolving solution, pentadecapeptide BPC 157 therapy, has been used in alleviating various vascular occlusion disturbances. BPC 157 was previously reviewed as novel mediator of Robert cytoprotection and endothelium protection in the stomach, and gut-brain axis, beneficial therapy in gastrointestinal tract, with particular reference to vascular recruitment, ulcerative colitis and tumor cachexia, and other tissues healing. Here we raised new hypothesis about BPC 157 therapy in the Budd-Chiari syndrome in rats, rapid bypassing of the suprahepatic inferior caval vein occlusion, and rats recovery with the active and effective pharmacotherapy treatment.
To investigate Budd-Chiari syndrome model (inferior caval vein suprahepatic occlusion) resolution, since BPC 157 resolves various rat vascular occlusion.
We assessed the activated bypassing pathways between the inferior and superior caval veins and portocaval shunt, counteracted caval/portal hypertension, aortal hypotension, venous/arterial thrombosis, electrocardiogram disturbances, liver and gastrointestinal lesions (., stomach and duodenum hemorrhages, in particular, congestion). Rats with suprahepatic occlusion of the inferior vena cava by ligation were medicated at 1 min, 15 min, 24 h, or 48 h post-ligation. Medication consisted of 10 µg/kg BPC 157, 10 ng BPC 157 or 5 mL/kg saline, administered once as an abdominal bath or intragastric application. Gross and microscopic observations were made, in addition to assessments of electrical activity of the heart (electrocardiogram), portal and caval hypertension, aortal hypotension, thrombosis, hepatomegaly, splenomegaly and venography. Furthermore, levels of nitric oxide, malondialdehyde in the liver and serum enzymes were determined.
BPC 157 counteracted increased P wave amplitude, tachycardia and ST-elevation, ., right heart failure from acute thrombotic coronary occlusion. The bypassing pathway of the inferior vena cava-azygos (hemiazygos) vein-superior vena cava and portocaval shunt occurred rapidly. Even with severe caval ˃ portal hypertension, BPC 157 antagonized portal and caval hypertension and aortal hypotension, and also reduced refractory ascites. Thrombosis of portal vein tributaries, inferior vena cava, and hepatic and coronary arteries was attenuated. In addition, there was reduced pathology of the lungs (severe capillary congestion) and liver (dilated central veins and terminal portal venules), decreased intestine hemorrhagic lesions (substantial capillary congestion, submucosal edema and architecture loss), and increased liver and spleen weight. During the period of ligation, nitric oxide- and malondialdehyde-levels in the liver remained within normal healthy values, and increases in serum enzymes were markedly reduced.
BPC 157 counteracts Budd Chiari syndrome in rats.
最近，作为一种可能的治疗解决方案，十五肽BPC 157疗法已被用于缓解各种血管阻塞性疾病。BPC 157先前被认为是胃、肠-脑轴中罗伯特细胞保护和内皮保护的新型介质，是胃肠道有益疗法，尤其适用于血管新生、溃疡性结肠炎和肿瘤恶病质以及其他组织愈合。在此，我们提出了关于BPC 157治疗大鼠布加综合征、快速绕过肝上下腔静脉阻塞以及通过积极有效的药物治疗使大鼠恢复的新假说。
研究布加综合征模型（肝上下腔静脉阻塞）的解决情况，因为BPC 157可解决各种大鼠血管阻塞问题。
我们评估了下腔静脉和上腔静脉之间以及门腔分流的激活旁路途径，抵消了腔静脉/门静脉高压、主动脉低血压、静脉/动脉血栓形成、心电图紊乱、肝脏和胃肠道病变（如胃和十二指肠出血，特别是充血）。通过结扎造成肝上下腔静脉阻塞的大鼠在结扎后1分钟、15分钟、24小时或48小时给药。药物包括10μg/kg BPC 157、10ng BPC 157或5mL/kg生理盐水，通过腹腔灌注或胃内给药一次性给予。除了评估心脏电活动（心电图）、门静脉和腔静脉高压、主动脉低血压、血栓形成、肝肿大、脾肿大和静脉造影外，还进行了大体和显微镜观察。此外，还测定了肝脏中一氧化氮、丙二醛水平以及血清酶水平。
BPC 157抵消了P波振幅增加、心动过速和ST段抬高，即急性血栓性冠状动脉阻塞导致的右心衰竭。下腔静脉-奇静脉（半奇静脉）-上腔静脉和门腔分流的旁路途径迅速出现。即使存在严重的腔静脉＞门静脉高压，BPC 157也能对抗门静脉和腔静脉高压以及主动脉低血压，还能减少顽固性腹水。门静脉分支、下腔静脉以及肝动脉和冠状动脉的血栓形成得到减轻。此外，肺部（严重毛细血管充血）和肝脏（中央静脉和终末门静脉小支扩张）的病理改变减轻，肠道出血性病变（大量毛细血管充血、黏膜下水肿和结构破坏）减少，肝脏和脾脏重量增加。在结扎期间，肝脏中的一氧化氮和丙二醛水平保持在正常健康值范围内，血清酶的升高明显降低。
BPC 157可对抗大鼠布加综合征。
