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Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME

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World Journal of Gastroenterology 2017年第29期23卷 5304-5312页

作者： Domagoj Drmic Danijela Kolenc Spomenko Ilic Lara Bauk Marko Sever Anita Zenko Sever Kresimir Luetic Jelena Suran sven seiwerth Predrag Sikiric Departments of Pharmacology and Pathology Medical Faculty University of Zagreb Faculty of Medicine J.J. Strossmayer University of Osijek

To counteract/reveal celecoxib-induced toxicity and NO system involvement. METHODSCelecoxib (1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157 (known to inhibit these lesions, 10 μg/kg, 10 ng/kg, or 1 ng/kg ip) and L-arginine (100 mg/kg ip), as well as NOS blockade [N(G)-nitro-L-arginine methyl ester (L-NAME)] (5 mg/kg ip) given alone and/or combined immediately after celecoxib. Gastrointestinal, liver, and brain lesions and liver enzyme serum values in rats were assessed at 24 h and 48 h thereafter. RESULTSThis high-dose celecoxib administration, as a result of NO system dysfunction, led to gastric, liver, and brain lesions and increased liver enzyme serum values. The L-NAME-induced aggravation of the lesions was notable for gastric lesions, while in liver and brain lesions the beneficial effect of L-arginine was blunted. L-arginine counteracted gastric, liver and brain lesions. These findings support the NO system mechanism(s), both NO system agonization (L-arginine) and NO system antagonization (L-NAME), that on the whole are behind all of these COX phenomena. An even more complete antagonization was identified with BPC 157 (at both 24 h and 48 h). A beneficial effect was evident on all the increasingly negative effects of celecoxib and L-NAME application and in all the BPC 157 groups (L-arginine + BPC 157; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157). Thus, these findings demonstrated that BPC 157 may equally counteract both COX-2 inhibition (counteracting the noxious effects of celecoxib on all lesions) and additional NOS blockade (equally counteracting the noxious effects of celecoxib + L-NAME). CONCLUSIONBPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs’ post-surgery application and NO system involvement.

关键词： BPC 157 Celecoxib L-arginine N(G)-nitro-L-arginine methyl ester Rats

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Counteraction of perforated cecum lesions in rats: Effects of pentadecapeptide BPC 157,L-NAME and L-arginine

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World Journal of Gastroenterology 2018年第48期24卷 5462-5476页

作者： Domagoj Drmic Mariam Samara Tinka Vidovic Dominik Malekinusic Marko Antunovic Borna Vrdoljak Jelena Ruzman Marija Milkovic Perisa Katarina Horvat Pavlov Jerusha Jeyakumar sven seiwerth Predrag Sikiric Departments of Pharmacology and Pathology Medical Faculty University of Zagreb

AIM To study the counteraction of perforated cecum lesion using BPC 157 and nitric oxide(NO) system *** Alongside with the agents' application(after 1 min, medication(/kg, 10 ml/2 min bath/rat) includes: BPC 157(10 μg), L-NAME(5 mg), L-arginine(100mg) alone or combined, and saline baths(controls)) on the rat perforate cecum injury, we continuously assessed the gross reappearance of the vessels(USB microcamera) quickly propagating toward the defect at the cecum surface, defect contraction, bleeding attenuation, MDA-and NO-levels in cecum tissue at 15 min, and severity of cecum lesions and adhesions at 1 and 7 d. RESULTS Post-injury, during/after a saline bath, the number of vessels was significantly reduced, the defect was slightly narrowed, bleeding was significant and MDA-levels increased and NO-levels decreased. BPC 157 bath: the vessel presentation was markedly increased, the defect was noticeably narrowed, the bleeding time was shortened and MDA-and NO-levels remained normal. L-NAME: reduced vessel presentation but not more than the control, did not change defect and shortened bleeding. L-arginine: exhibited less vessel reduction, did not change the defect and prolonged bleeding. In combination, mutual counteraction occurred(L-NAME + L-arginine) or the presentation was similar to that of BPC 157 rats(BPC 157 + L-NAME; BPC 157 + L-arginine; BPC 157 + L-NAME + L-arginine), except the defect did not change. Thereby at day 1 and 7, saline, L-NAME, L-arginine and L-NAME + L-arginine failed(defect was still open and large adhesions present). CONCLUSION The therapeutic effect was achieved with BPC 157 alone or in combination with L-NAME and L-arginine as it was able to consolidate the stimulating and inhibiting effects of the NO-system towards more effective healing recruiting vessels.

关键词： BPC 157 perforated cecum L-arginine L-NAME vessels rats

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Gastric pentadecapeptide BPC 157 in cytoprotection to resolve major vessel occlusion disturbances,ischemia-reperfusion injury following Pringle maneuver,and Budd-Chiari syndrome

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World Journal of Gastroenterology 2022年第1期28卷 23-46页

作者： Predrag Sikiric Anita Skrtic Slaven Gojkovic Ivan Krezic Helena Zizek Eva Lovric Suncana Sikiric Mario Knezevic Sanja Strbe Marija Milavic Antonio Kokot Alenka Boban Blagaic sven seiwerth Department of Pharmacology School of MedicineUniversity of ZagrebZagreb 10000Croatia Department of Pathology School of MedicineUniversity of ZagrebZagreb 10000Croatia Department of Anatomy and Neuroscience Faculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijek 31000Croatia

The stable gastric pentadecapeptide BPC 157 counteracts various venous occlusion-induced *** are all these arguments,in the Robert’s cytoprotection concept terms,to substantiate the resolution of different major vessel occlusion disturbances,in particular ischemia-reperfusion injury following the Pringle maneuver and Budd-Chiari syndrome,which was obtained by BPC 157 ***,there is new point(bypassed occluded or ruptured vessel,the equation endothelium maintenance→epithelium maintenance=blood vessel recruitment and activation towards defect or bypassing vessel occlusion),the recruitment of collateral blood vessels to compensate for vessel occlusion and reestablish blood *** this paper,we summarize the evidence of the native cytoprotective gastric pentadecapeptide BPC 157,which is stable in the human gastric juice,is a membrane stabilizer and counteracts gut-leaky *** a particular target,it is distinctive from the standard peptide growth factors,with particular molecular pathways involved,controlling VEGF and NO *** the early 1990s,BPC 157 appeared as a late outbreak of the Robert’s and Szabo’s cytoprotection-organoprotection concept,epithelium,endothelium protection as previous theoretical/practical breakthrough in the 1980s,and brain-gut axis and gut-brain *** the time went on,with its reported effects,it is likely most useful theory practical implementation and ***,several reviews suggest that BPC 157,which does not have a lethal dose(LD1),has profound cytoprotective activity,used to be demonstrated in ulcerative colitis and invented to multiple sclerosis ***,it may bring the theory to practical application,starting with the initial argument,no degradation in human gastric juice for more than 24 h,and thereby,the therapeutic effectiveness(including therapeutic per-oral regimen)and pleiotropic beneficial effects.

关键词： Gastric pentadecapeptide BPC 157 Cytoprotection Major vessel occlusion disturbances Pringle maneuver Budd-Chiari syndrome Therapy

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Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME

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World Journal of Gastroenterology 2016年第41期22卷 9127-9140页

作者： Zeljko Djakovic Ivka Djakovic Vedran Cesarec Goran Madzarac Tomislav Becejac Goran Zukanovic Domagoj Drmic Lovorka Batelja Anita Zenko Sever Danijela Kolenc Alen Pajtak Nikica Knez Mladen Japjec Kresimir Luetic Dinko Stancic-Rokotov sven seiwerth Predrag Sikiric Departments of Pharmacology and Pathology Medical Faculty University of Zagreb 10000 Zagreb Croatia

AIM To cure typically life-threatening esophagogastric anastomosis in rats, lacking anastomosis healing and sphincter function rescue, in particular. METHODS Because we assume esophagogastric fistulas represent a particular NO-system disability, we attempt to identify the benefits of anti-ulcer stable gastric pentadecapeptide BPC 157, which was in trials for ulcerative colitis and currently for multiple sclerosis, in rats with esophagocutaneous fistulas. Previously, BPC 157 therapies have promoted the healing of intestinal anastomosis and fistulas, and esophagitis and gastric lesions, along with rescued sphincter function. Additionally, BPC 157 particularly interacts with the NOsystem. In the 4 d after esophagogastric anastomosis creation, rats received medication(/kg intraperitoneallyonce daily: BPC 157(10 μg, 10 ng), L-NAME(5 mg), or L-arginine(100 mg) alone and/or combined or BPC 157(10 μg, 10 ng) in drinking water). For rats underwent esophagogastric anastomosis, daily assessment included progressive stomach damage(sum of the longest diameters, mm), esophagitis(scored 0-5), weak anastomosis(m L H2 O before leak), low pressure in esophagus at anastomosis and in the pyloric sphincter(cm H2O), progressive weight loss(g) and mortality. Immediate effect assessed blood vessels disappearance(scored 0-5) at the stomach surface immediately after anastomosis creation. RESULTS BPC 157(all regimens) fully counteracted the perilous disease course from the very beginning(i.e., with the BPC 157 bath, blood vessels remained present at the gastric surface after anastomosis creation) and eliminated mortality. Additionally, BPC 157 treatment in combination with L-NAME nullified any effect of L-NAME that otherwise intensified the regular course. Consistently, with worsening(with L-NAME administration) and amelioration(with L-arginine), either L-arginine amelioration prevails(attenuated esophageal and gastric lesions) or they counteract each other(L-NAME + L-arginine); with the addi

关键词： Esophagogastric anastomosis L-NAME Aggravation BPC 157 L-arginine Curative treatment Rats

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Stomach perforation-induced general occlusion/occlusion-like syndrome and stable gastric pentadecapeptide BPC 157 therapy effect

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World Journal of Gastroenterology 2023年第27期29卷 4289-4316页

作者： Luka Kalogjera Ivan Krezic Ivan Maria Smoday Hrvoje Vranes Helena Zizek Haidi Yago Katarina Oroz Vlasta Vukovic Ivana Kavelj Luka Novosel Slavica Zubcic Ivan Barisic Lidija Beketic Oreskovic Sanja Strbe Marko Sever Ivica Sjekavica Anita Skrtic Alenka Boban Blagaic sven seiwerth Predrag Sikiric Department of Pharmacology School of MedicineZagreb 10000Croatia Division of Oncology and Radiotherapy University Hospital for TumorsSestre milosrdnice University Hospital CentreZagreb 10000Croatia Department of Pathology School of MedicineZagreb 10000Croatia

BACKGROUND Using rat stomach perforation as a prototypic direct lesion applied in cytoprotection research,we focused on the first demonstration of the severe occlusion/occlusion-like syndrome induced by stomach *** revealed stomachinduced occlusion/occlusion-like syndrome corresponds to the previously described occlusion/occlusion-like syndromes in rats suffering multicausal pathology and shared severe vascular and multiorgan *** general point was particularly *** in all the described occlusion/occlusion-like syndromes with permanent occlusion of major vessels,peripheral and central,and other similar noxious procedures that severely affect endothelium function,the stable gastric pentadecapeptide BPC 157 was resolving *** To reveal the stomach perforation-induced general occlusion/occlusion-like syndrome and BPC 157 therapy *** The procedure included deeply anesthetized rats,complete calvariectomy,laparotomy at 15 min thereafter,and stomach perforation to rapidly induce vascular and multiorgan failure occlusion/occlusion-like *** 5 min post-perforation time,rats received therapy[BPC 157(10μg or 10 ng/kg)or saline(5 mL/kg,1 mL/rat)(controls)]into the perforated defect in the stomach).Sacrifice was at 15 min or 60 min post-perforation ***(gross and microscopy;volume)included:Brain swelling,peripheral vessels(azygos vein,superior mesenteric vein,portal vein,inferior caval vein)and heart,other organs lesions(i.e.,stomach,defect closing or widening);superior sagittal sinus,and peripherally the portal vein,inferior caval vein,and abdominal aorta blood pressures and clots;electrocardiograms;and bleeding time from the perforation(s).RESULTS BPC 157 beneficial effects accord with those noted before in the healing of the perforated defect(raised vessel presentation;less bleeding,defect contraction)and occlusion/occlusion-like syndromes *** 157 therapy(into the perforated defect),induced immediate

关键词： Stomach perforation General occlusion/occlusion-like syndrome Stable gastric pentadecapeptide BPC 157 Cytoprotection Therapy Rats

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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

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World Journal of Gastroenterology 2018年第47期24卷 5366-5378页

作者： Fedor Amic Domagoj Drmic Zdenko Bilic Ivan Krezic Helena Zizek Marina Peklic Robert Klicek Alen Pajtak Enio Amic Tinka Vidovic Mislav Rakic Marija Milkovic Perisa Katarina Horvat Pavlov Antonio Kokot Ante Tvrdeic Alenka Boban Blagaic Mario Zovak sven seiwerth Predrag Sikiric Department of Pharmacology Medical Faculty University of Zagreb Department of Pathology Medical Faculty University of Zagreb

AIM To investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide(NO) system *** 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 *** 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 *** BPC 157, rapidly bypassing occlusion, rescued the original duodenal flow through IAPDV to SMV flow, aneffect related to the NO system and

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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Circular gastrotomy in rat:a new healing model. Stable gastric pentade-capeptide BPC 157, atropine, cimetidine,omeprazole

Circular gastrotomy in rat:a new healing model. Stable gastr...

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第十五届国际药理学大会

作者： Zoricic Ivan Sever Marko Radic Bozo Jakir Ana Brcic Luka Anic Tomislav seiwerth sven Sikiric Predrag Medical Faculty Medical Faculty Medical Faculty Medical Faculty Medical Faculty Medical Faculty Medical Faculty Medical Faculty

＜正＞ Like gastric folds for stomach integrity, large flat areas without any fold could be particular for injured stomach and muscle damage. Circular gastrotomy was at 1cm bellow rat cardia. only 5mm at small curvature remained intact. Therapy （mg/kg）（gastric pentadecapeptide BPC 157 （in IBD. PLD - 116. Pliva. Croatia）（0.01）. cimetidine （50）. atropine（10）. omeprazole （50）） was i.p. once daily, first immediately after surgery, last at 24h before sacrifice （at 1h. 2h. 6h. 24h. 5 days. 7 days. 14 days）. Results. Largely flatted stomach and only 40% area with thin gastric folds are along with poor healing of transected muscle, grossly and microscopically. Also, desmin immunohistochemistry/muscle regeneration shows sharp demarcation of positive fibers on the musclegranulation tissue border with only very scant immunoreactivity in vessel walls in the granulation tissue. All agents improved folds presentation, but only BPC 157 approaches to nearly 100%. with desmin immunoreactive cell clusters （muscle regeneration） penetrating the granulation tissue, and stronger immunoreactivity in vessel walls throughout the granulation tissue. Conclusion. BPC 157 is valuable for major stomach resection.

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Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights

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World Journal of Gastroenterology 2017年第48期23卷 8465-8488页

作者： Antonija Duzel Josipa Vlainic Marko Antunovic Dominik Malekinusic Borna Vrdoljak Mariam Samara Slaven Gojkovic Ivan Krezic Tinka Vidovic Zdenko Bilic Mario Knezevic Marko Sever Nermin Lojo Antonio Kokot Marijan Kolovrat Domagoj Drmic Jaksa Vukojevic Tamara Kralj Katarina Kasnik Marko Siroglavic sven seiwerth Predrag Sikiric Departments of Pharmacology and Pathology Medical Faculty University of Zagreb Medical Faculty J.J.Strossmayer University of Osijek OsijekCroatia Rudjer Boskovic Institute Department of Molecular Medicine

AIM To provide new insights in treatment of colitis and ischemia and reperfusion in rats using stable gastric pentadecapeptide BPC 157. METHODS Medication [BPC 157,L-NAME,L-arginine(alone/combined),saline] was bath at the blood deprived colon segment. During reperfusion,medication was BPC 157 or saline. We recorded(USB microscope camera) vessel presentation through next 15 min of ischemic colitis(ICrats) or reperfusion(removed ligations)(IC + RL-rats);oxidative stress as MDA(increased(IC-and IC + RLrats)) and NO levels(decreased(IC-rats);increased(IC + RL-rats)) in colon tissue. IC + OB-rats [IC-rats had additional colon obstruction(OB)] for 3 d(IC + OBrats),then received BPC 157 bath. RESULTS Commonly,in colon segment(25 mm,2 ligations on left colic artery and vein,3 arcade vessels within ligated segment),in IC-,IC + RL-,IC + OB-rats,BPC 157(10 μg/kg) bath(1 m L/rat) increased vessel presentation,inside/outside arcade interconnections quickly reappeared,mucosal folds were preserved and the pale areas were small and markedly reduced. BPC 157 counteracted worsening effects induced by L-NAME(5 mg) and L-arginine(100 mg). MDA-and NO-levels were normal in BPC 157 treated IC-rats and IC + RLrats. In addition,on day 10,BPC 157-treated IC + OBrats presented almost completely spared mucosa with very small pale areas and no gross mucosal defects;the treated colon segment was of normal diameter,and only small adhesions were *** BPC 157 is a fundamental treatment that quickly restores blood supply to the ischemically injured area and rapidly activates collaterals. This effect involves the NO system.

关键词： Ischemic colitis Blood flow rescue Collaterals BPC 157 L-NAME L-arginine Oxidative stress NO Rats

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Pentadecapeptide BPC 157 resolves Pringle maneuver in rats,both ischemia and reperfusion

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World Journal of Hepatology 2020年第5期12卷 184-206页

作者： Marijan Kolovrat Slaven Gojkovic Ivan Krezic Dominik Malekinusic Borna Vrdoljak Katarina Kasnik Kovac Tamara Kralj Domagoj Drmic Ivan Barisic Katarina Horvat Pavlov Andreja Petrovic Antonija Duzel Mario Knezevic Ivan Mirkovic Antonio Kokot Alenka Boban Blagaic sven seiwerth Predrag Sikiric Departments of Pharmacology and Pathology School of MedicineUniversity of ZagrebZagreb 10000Croatia

BACKGROUND The Pringle maneuver[portal triad obstruction(PTO)]provides huge disturbances during ischemia and even more thereafter in ***,a possible solution may be stable gastric pentadecapeptide BPC 157,with already documented beneficial effects in ischemia/reperfusion ***,BPC 157,as a cytoprotective agent,successfully resolved vessel occlusions in rats(ischemic colitis;deep vein thrombosis,superior anterior pancreaticoduodenal vein;bile duct cirrhosis)through rapid collateral vessel recruitment to circumvent vessel ***,medication BPC 157 regimens were administered as a single challenge before and during ischemia or,alternatively,at various time points during *** To introduce BPC 157 therapy against pringle *** In deeply anesthetised rats,the portal triad was clamped up for 30 *** then underwent reperfusion for either 15 min or 24 ***[(10μg,10 ng/kg)regimens,administered as a single challenge]picked(a)ischemia,PTO period[at 5 min before(ip)or at 5 or 30 min of ligation time(as a bath to PTO)]or(b)reperfusion,post-PTO period[at 1 or 15 min(bath during surgery)or 24 h(ip)reperfusion-time].We provided gross,microscopy,malondialdehyde,serum enzymes,electrocardiogram,portal,caval,and aortal pressure,thrombosis and venography *** BPC 157 counteracts electrocardiogram disturbances(increased P wave amplitude,S1Q3T3 QRS pattern and tachycardia).Rapidly presented vascular pathway(portal vein-superior mesenteric vein-inferior mesenteric vein-rectal veins-left ileal vein-inferior caval vein)as the adequate shunting immediately affected disturbed *** hypertension and severe aortal hypotension during PTO,as well as portal and caval hypertension and mild aortal hypotension in reperfusion and refractory ascites formation were markedly attenuated(during PTO)or completely abrogated(reperfusion);thrombosis in portal vein tributaries and inferior caval vein o

关键词： BPC 157 Pringle maneuver Rats Portal hypertension Caval hypertension Ischemia

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Bowel adhesion and therapy with the stable gastric pentadecapeptide BPC 157,L-NAME and L-arginine in rats

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2020年第5期11卷 93-109页

作者： Lidija Berkopic Cesar Slaven Gojkovic Ivan Krezic Dominik Malekinusic Helena Zizek Lovorka Batelja Vuletic Andreja Petrovic Katarina Horvat Pavlov Domagoj Drmic Antonio Kokot Josipa Vlainic sven seiwerth Predrag Sikiric Department of Pharmacology School of MedicineUniversity of ZagrebZagreb 10000Croatia Department of Pathology School of MedicineUniversity of ZagrebZagreb 10000Croatia Institute Ruder Boskovic Zagreb 10000Croatia

BACKGROUND After parietal peritoneum excision with an underlying superficial layer of muscle tissue in rats,there is failed vasculature,and finally,increased adhesion *** 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 *** To focused on the bowel adhesion and the therapy with the BPC 157,its most and application of *** 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(10μg/kg,10 ng/kg,1 mL/rat),an equivolume of saline,L-NAME(5 mg/kg),L-arginine(200 mg/kg)alone and/or ***,medication was(2)intraperitoneally once daily,first application at 30 min after surgery,last application 24 h before assessment at d 7 or d *** a postponed therapy to preexisting adhesion(3),BPC 157(10μg/kg,10 ng/kg intraperitoneally,1 mL/rat)was given once daily since d *** recovery effect of the BPC 157 regimens goes with the presence of abundant vascular vessels in and near the defect,which occurs ***,also applied as post-treatment,BPC 157 creates attenuated adhesions,minimal or no ***,NO-agents have diverse initial and final effects:The initial weakening of blood vessel disappearance and finally,severe worsening of adhesions(LNAME)vs the initial weakening of blood vessel disappearance and finally,attenuation of adhesions formation(L-arginine),which counteract each other response given ***,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 MDAvalues-adhesion tissue formation relation,unlike diverse effect of the NO-agents,the BPC 157 application effect regularly

关键词： Abdominal wall defect Adhesions BPC 157 Vascular recruitment Nitric oxide-agents Rats

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