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Bypassing major venous occlusion and duodenal lesions in rats, and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine

查看全文 作　　者：Fedor [1,2]Amic;Domagoj [1,2]Drmic;Zdenko [1,2]Bilic;Ivan [1,2]Krezic;Helena [1,2]Zizek;Marina [1,2]Peklic;Robert [1,2]Klicek;Alen [1,2]Pajtak;Enio [1,2]Amic;Tinka [1,2]Vidovic;Mislav [1,2]Rakic;Marija Milkovic [1,2]Perisa;Katarina Horvat [1,2]Pavlov;Antonio [1,2]Kokot;Ante [1,2]Tvrdeic;Alenka Boban [1,2]Blagaic;Mario [1,2]Zovak;Sven [1,2]Seiwerth;Predrag [1,2]Sikiric 高影响力作者 机构地区：[1]Department of Pharmacology, Medical Faculty, University of Zagreb;[2]Department of Pathology, Medical Faculty, University of Zagreb高影响力机构 出　　处：《World Journal of Gastroenterology》索引2018年第24卷第47期,共13页高影响力期刊 摘　　要：AIM To investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide(NO) system involvement.METHODS Male Wistar rats underwent superior anterior pancreaticoduodenal vein(SAPDV)-ligation and were treated with a bath at the ligated SAPDV site(BPC 157 10 μg, 10 ng/kg per 1 mL bath/rat; L-NAME 5 mg/kg per 1 m L bath/rat; L-arginine 100 mg/kg per 1 mL bath/rat, alone and/or together; or BPC 157 10 μg/kg instilled into the rat stomach, at 1 min ligation-time). We recorded the vessel presentation(filled/appearance or emptied/disappearance) between the 5 arcade vessels arising from the SAPDV on the ventral duodenum side, the inferior anterior pancreaticoduodenal vein(IAPDV) and superior mesenteric vein(SMV) as bypassing vascular pathway to document the duodenal lesions presentation; increased NO-and oxidative stress [malondialdehyde(MDA)]-levels in duodenum.RESULTS Unlike the severe course in the SAPDV-ligated controls, after BPC 157 application, the rats exhibited strong attenuation of the mucosal lesions and serosal congestion, improved vessel presentation, increased interconnections, increased branching by more than 60% from the initial value, the IAPDV and SMV were not congested. Interestingly, after 5 min and 30 min of L-NAME and L-arginine treatment alone, decreased mucosal and serosal duodenal lesions were observed; their effect was worsened at 24 h, and no effect on the collateral vessels and branching was seen. Together, L-NAME+L-arginine antagonized each other's response, and thus, there was an NO-related effect. With BPC 157, all SAPDV-ligated rats receiving L-NAME and/or L-arginine appeared similar to the rats treated with BPC 157 alone. Also, BPC 157 in SAPDV-ligated rats normalized levels of NO and MDA, two oxidative stress markers, in duodenal tissues.CONCLUSION BPC 157, rapidly bypassing occlusion, rescued the original duodenal flow through IAPDV to SMV flow, aneffect related to the NO system and reduction of free radical formation. 关 键 词：MAJOR venous occlusion DUODENAL LESIONS BPC 157 L-NAME Bypassing L-ARGININE Reduction of free radical formation RATS
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