The effect of platelet activating factor antagonist (BN 52021) on cerulein-induced acute pancreatitis with reference to oxygen radicals

Acute edematous pancreatitis was induced in Wistar male rats by iv infusion of cerulein (CR) in the dose of 5.10(-6)g.kg-1.h-1 during 3 or 6 h. The effect of BN 52021--platelet activating factor (PAF) receptor antagonist, against this model of disease was examined. BN 52021 was applied iv as a bolus injection in the dose of 5.10(-3)g.kg-1 at 0 time. Treatment with this agent significantly ameliorates cerulein-induced acute pancreatitis in rats. The effect of BN 52021 was expressed by significant reduction of pancreas edema, diminution of hyperamylasemia, lack of superoxide dismutase activity depletion, and inhibition of lipid peroxidation in pancreatic tissue. These changes were accompanied by significant reduction of acinar cells vacuolization and remarkable inhibition of infiltration with inflammatory cells in the interacinar space. We suppose that beneficial effect of BN 52021 against cerulein-induced acute pancreatitis in rats depends on the prevention of inflammatory cells activation and subsequent generation of oxygen radicals within pancreatic tissue.     

The effect of platelet activating factor antagonist (BN 52021) on cerulein-induced acute pancreatitis with reference to oxygen radicals

Acute edematous pancreatitis was induced in Wistar male rats by iv infusion of cerulein (CR) in the dose of 5.10^-6g.kg^-1.h^-1 during 3 or 6 h. The effect of BN 52021—platelet activating factor (PAF) receptor antagonist, against this model of disease was examined. BN 52021 was applied iv as a bolus injection in the dose of 5.10^-3g.kg^-1 at 0 time. Treatment with this agent significantly ameliorates cerulein-induced acute pancreatitis in rats. The effect of BN 52021 was expressed by significant reduction of pancreas edema, diminution of hyperamylasemia, lack of superoxide dismutase activity depletion, and inhibition of lipid peroxidation in pancreatic tissue. These changes were accompanied by significant reduction of acinar cells vacuolization and remarkable inhibition of infiltration with inflammatory cells in the interacinar space. We suppose that beneficial effect of BN 52021 against cerulein-induced acute pancreatitis in rats depends on the prevention of inflammatory cells activation and subsequent generation of oxygen radicals within pancreatic tissue.     

血小板活化因子在急性胰腺炎大鼠并发肾损伤中病理生理作用

目的:本文旨在观察血小板活化因子在急性出血坏死性胰腺炎(AHNP)大鼠肾损伤发生中作用。方法:159只SD大鼠随机分三组:假手术组、AHNP非治疗组和AHNP BN(52021)治疗祖。采用胰管内注入5％牛磺胆酸钠溶液诱导大鼠AHNP,应用~(86)Rb组织摄取法测定肾脏相对血流量及组织灌注量,并测定血小板聚集率(PAgR)。结果:与非治疗组相比较,BN(52021)治疗组肾脏相对血流量、组织灌注量显著提高;PAgR下降;肾脏病理损害减轻。结论:血小板活化因子参与了急性出血坏死性胰腺炎大鼠肾损害的发生。     

Mechanism and dose-effect of Ginkgolide B on severe acute pancreatitis of rats

AIM:To determine the optimal dosage and mechanism of Ginkgolide B(BN52021) on severe acute pancreatitis(SAP) of rats.METHODS:Seventy male Wistar rats were randomly divided into seven groups(10 for each group).Shamoperation group(SO),SAP model group(SAP),dimethyl sulfoxide(DMSO) contrast group(DMSO),and groups treated with 2.5 mg/kg BN52021(BN1),5 mg/kg BN52021(BN2),10 mg/kg BN52021(BN3),and 20 μg/kg Sandostatin(SS).The SAP model was established in Wistar rats by injecting 5% sodium taurocholate retrogradely...     

Effect of BN52021 on NFκ-Bp65 expression in pancreatic tissues of rats with severe acute pancreatitis

AIM： To investigate dynamic changes and significance of expression of NF-κBp65 in pancreatic tissues of rats with severe acute pancreatitis （SAP）, as well as BN52021 effects.
METHODS： Wistar male rats were randomly divided into negative control group （NC group, n = 60）, SAP-model group （SAP group, n = 60）, and BN52021-treated group （BN group, n = 60）, and each of the above groups was respectively divided into 6 subgroups at different time points after operation （1 h, 2 h, 3 h, 6 h, 12 h, and 24 h） （n = 10）. By RT-PCR and Western blot, NF-κBp65 mRNA and its protein expression in pancreatic tissues of rats were detected respectively.
RESULTS： The expression of NF-κBp65 mRNA dynamically changed in both SAP groups and BN groups. The mRNA level was higher in SAP groups than NC groups at 2 h, 3 h, 12 h, and 24 h after operation （P 〈 0.05）, higher in BN groups than NC groups at all time points （P 〈 0.05）, and higher in BN groups than SAP group at 1 h （P 〈 0.05）. The NF-κBp65 protein level was higher in SAP groups than NC groups at 1 h, 3 h, and 6 h （P 〈 0.01）, and 2 h, 12 h, and 24 h （P 〈 0.05）, higher in BN groups than NC groups at all time points （P 〈 0.05）, and lower in BN groups than SAP groups at 1 h, 3 h, and 6 h （P 〈 0.05）.
CONCLUSION： The expression of NF-κBp65 in pancreatic tissues is dynamically changed and the changes play an important role in pathogenesis of SAR BN52021 exerts therapeutic effects through reducing the expression level of NF-κBp65 protein in the early stage of SAR     

Effect of BN52021 on NFκ-Bp65 expression in pancreatic tissues of rats with severe acute pancreatitis

AIM: To investigate dynamic changes and significance of expression of NF-κBp65 in pancreatic tissues of rats with severe acute pancreatitis (SAP), as well as BN52021 effects.METHODS: Wistar male rats were randomly divided into negative control group (NC group, n = 60), SAP-model group (SAP group, n = 60), and BN52021-treated group (BN group, n = 60), and each of the above groups was respectively divided into 6 subgroups at different time points after operation (1 h, 2 h, 3 h, 6 h, 12 h, and 24 h) (n = 10). By RT-PCR and Western blot, NF-KBp65 mRNA and its protein expression in pancreatic tissues of rats were detected respectively.RESULTS: The expression of NF-KBp65 mRNA dynamically changed in both SAP groups and BN groups. The mRNA level was higher in SAP groups than NC groups at 2 h, 3 h, 12 h, and 24 h after operation (P < 0.05), higher in BN groups than NC groups at all time points (P < 0.05), and higher in BN groups than SAP group at 1 h (P < 0.05). The NF-jcBp65 protein level was higher in SAP groups than NC groups at 1 h, 3 h, and 6 h (P < 0.01), and 2 h, 12 h, and 24 h (P < 0.05), higher in BN groups than NC groups at all time points (P < 0.05), and lower in BN groups than SAP groups at 1 h, 3 h, and 6 h (P < 0.05).CONCLUSION: The expression of NF-icBp65 in pancreatic tissues is dynamically changed and the changes play an important role in pathogenesis of SAP. BN52021 exerts therapeutic effects through reducing the expression level of NF-κBp65 protein in the early stage of SAP.     

银杏苦内酯B对急性坏死性胰腺炎大鼠肺组织PAF—R表达的影响

目的观测银杏苦内酯B（BN52021）干预前后ANP大鼠肺组织血小板活化因子受体（PAF-R）mRNA和蛋白质表达的变化,探讨其作用机制。方法180只大鼠随机分为对照组（NC组）、ANP组和BN52021治疗组（BN组）,每组再分为制模后1h、2h、3h、6h、12h、24h6个亚组。逆行胰胆管内注射牛磺胆酸钠诱导ANP。BN组于制模后15min股静脉注入BN52021（0.5mg/100g体重）。各时间点取血检测血清淀粉酶,取胰腺和肺组织行病理学检查,采用RT-PCR和Western blot检测肺组织PAF-R mRNA和蛋白质表达。结果ANP组和BN组各时点血清淀粉酶均高于NC组（P〈0.05）,BN组1h、2h、3h、6h、24h时点均低于ANP组（P〈0.05）。ANP组和BN组胰腺和肺的病理分值均高于NC组,BN组在3h、6h、12h显著低于ANP组（P〈0.05）。ANP组和BN组PAF-R mRNA和蛋白质水平分别在3h和1h显著高于NC组,BN组与ANP组相比无显著差异。结论PAF-R在ANP早期急性肺损伤中起重要作用,BN52021对其表达无显著影响。     

Significance of platelet activating factor receptor expression in pancreatic tissues of rats with severe acute pancreatitis and effects of BN52021

AIM:To investigate the dynamic changes and significance of platelet activating factor receptor (PAF-R) mRNA and protein in pancreatic tissues of rats with severe acute pancreatitis (SAP) and effects of BN52021 (Ginkgolide B). METHODS:Wistar male rats were randomly assigned to the negative control group (NC group),SAP model group (SAP group),and BN52051-remedy group (BN group),and each of the groups was divided into 6 subgroups at different time points after operation (1 h,2 h,3 h,6 h,12 h,and 24 h) (n=10 in each). PT-PCR and Western blot methods were used to detect PAF-RmRNA and protein expression in pancreatic tissues of rats respectively. Pathological examination of pancreatic tissues was performed and the serum amylase change was detected. RESULTS:Serum amylase and pathological results showed the that SAP model was successfully prepared,BN52021 was able to decrease serum amylase,and the pathological ratings in BN group at 3 h,6 h,and 12 h significantly decreased compared with those in the SAP group (8.85 ± 0.39 vs 5.95 ± 0.19,9.15 ± 0.55 vs 5.55 ± 0.36,10.10 ± 0.65 vs 6.72 ± 0.30,P < 0.05). The result of PAF-mRNA showed dynamic changes in SAP and BN groups,which increased gradually in early stage,reached a peak at 3 h (0.71 ± 0.14 vs 0.54 ± 0.14,0.69 ± 0.13 vs 0.59 ± 0.04,P < 0.05),and decreased gradually later. There were significant differences at each time point except 1 h and 2 h,when compared with those in the NC group (0.71 ± 0.14 or 0.69 ± 0.13 vs 0.47 ± 0.10,0.38 ± 0.08 or 0.59 ± 0.04 vs 0.47 ± 0.09,0.25 ± 0.07 or 0.29 ± 0.05 vs 0.46 ± 0.10,0.20 ± 0.06 or 0.20± 0.04 vs 0.43 ± 0.09,P < 0.05),whereas there was no significant difference between BN and SAP groups at each time point. The result of PAF-R protein showed that the change of PAF-R protein in the SAP group and the BN group was consistent with that of PAF-R mRNA. There were significant differences at each time point except 1 h,when compared with those in the NC group (0.90 ± 0.02 or 0.80 ± 0.05 vs 0.48 ± 0.02,1.69 ± 0.06 or 1.58 ± 0.02 vs 0.48 ± 0.03,1.12 ± 0.10 or 0.98 ± 0.03 vs 0.49 ± 0.09,1.04 ± 0.14 or 0.87 ± 0.02 vs 0.52 ± 0.08,0.97 ± 0.16 or 0.90 ± 0.05 vs 0.49 ± 0.10,P < 0.05),whereas there was no significant difference between the BN group and the SAP group. CONCLUSION:PAF-R plays an important role in occurrence and development of SAP. BN52021 exerts biological effects through competitively inhibiting the binding of increased both PAF and PAF-R expression rather than through decreasing PAF-R expression in pancreatic tissues.     

Role of platelet-activating factor in hemodynamic derangements in an acute rodent pancreatic model.

Systemic hemodynamics were assessed in a model of experimental pancreatitis induced in rats by the retrograde injection of sodium deoxycholate, 40%, 1 mL/kg, in the pancreatic duct, using the radioactive microsphere technique before and 25 minutes after pancreatitis induction while blood pressure was stable (n = 10). A 55% decrease in cardiac out-put, a 14% decrease in heart rate, and a 3.3-fold increase in total peripheral resistances, without significant changes in blood pressure, were observed. Renal blood flow decreased by 68%. When rats were given BN-52021, a blocker of platelet-activating factor receptors (5 mg/h, IV; n = 13) coinciding with pancreatitis induction, no significant hemodynamic changes were observed. Animals treated with BN-52021 survived 89 +/- 10 minutes, whereas death occurred 67 +/- 5 minutes after pancreatitis induction in untreated rats (P less than 0.001). A different group of rats with pancreatitis showed higher blood levels of platelet-activating factor (0.28 +/- 0.06 ng/mL; n = 11) than control rats (0.16 +/- 0.03; n = 15; P less than 0.05). Very high levels of platelet-activating factor were found in peritoneal exudate from rats with pancreatitis. These data show an effective protective effect of BN-52021 on the hemodynamic impairment that follows pancreatitis induction, as well as a role of platelet-activating factor in these alterations.     

Effects of octreotide in acute hemorrhagic necrotizing pancreatitis in rats

BACKGROUND AND AIM: Octreotide is considered to reduce exocrine pancreatic secretion in acute hemorrhagic necrotizing pancreatitis decreasing pancreatic autodigestion. The aim of this study was to determine whether octreotide also has antioxidative effects in acute pancreatitis. Additionally time and dose of application were of interest. METHOD: Ninety male Sprague-Dawley rats were randomized into six groups (n = 15). Group 1 underwent a laparotomy, and animals in groups 2-6 received intraductal glycodeoxycholic acid followed by intravenous cerulein. Groups 3 and 4 were injected with 0.5 mg octreotide, while groups 5 and 6 received continuous intravenous infusion of 0.05 mg octreotide/h for 10 h. Treatment was initiated 6 hours after induction of pancreatitis (IP) in groups 3 and 5, and 14 h after IP in groups 4 and 6. At 24 h after IP all animals were killed and each pancreas was analyzed histopathologically. In addition, levels of pancreatic lipid peroxidation protective enzymes glutathione-peroxidase (GSH-Px) and superoxide dismutase (SOD) as well as lipid peroxidation via thiobarbituric acid reactive substances (TBARS) were determined. RESULTS: Early bolus application of octreotide reduced severity of histopathological changes in acute pancreatitis and decreased lipid peroxidation in pancreatic tissue samples; however, late bolus application and continuous intravenous infusion did not influence pancreatitis or lipid peroxidation. CONCLUSION: Octreotide seems to have a dose- and time-dependent effect on histopathology and lipid peroxidation in a model of pancreatitis in rats.     

Oxygen-derived free radicals in cerulein-induced acute pancreatitis

Conscious rats were treated with a supramaximal dose of 5.10(-6)g.kg-1.h-1 of cerulein for periods of 3 and 12 h. In both groups of animals typical features of acute oedematous pancreatitis were proved by biochemical and histologic examinations. The most important finding of our study was the decrease of superoxide dismutase (SOD) activity in pancreatic tissue, accompanied by a slight increase of this scavenger enzyme in serum of rats stimulated with cerulein during 3 h. Parallelly, evident elevation of malondialdehyde (MDA) concentration in pancreatic tissue was noted. After the 12-h infusion of cerulein we were not able to detect any SOD activity in pancreatic tissue, whereas this activity appeared in ascitic fluid of tested animals. Further increase of MDA concentration in pancreatic tissue, in comparison with 3-h pancreatitis, was found. These data suggest that in 3-h and 12-h cerulein-induced pancreatitis the oxygen-derived free radicals mediate the increased lipid peroxidation in pancreatic tissue. We think that the depletion of the scavenger enzyme SOD may be responsible for such a disturbance of lipid metabolism.     

急性出血坏死性胰腺炎大鼠肠粘膜病变的实验研究

以胆胰管内注入牛磺胆酸钠诱发大鼠急性出血坏死性胰腺炎（ＡＨＮＰ）模型。术后１、６、１２小时应用８６ＲｂＣｌ标记法动态测定空回肠血流量；取回肠标本小块作光镜、扫描和透视电镜观察；同时观察ＮＢ５２０２１、Ｄａｚｍｅｇｒｅｌ对上述指标的影响。结果表明ＡＨＮＰ模型制备后，肠粘膜病理损伤呈时间依赖性，术后１２小时呈显著的粘膜下水肿、绒毛脱落裸露、上皮细胞间桥粒断裂；肠血流量进行性下降；ＢＮ５２０２１、Ｄａｚｍｅｇｒｅｌ显著增加肠血流量，减轻肠粘膜病理损伤。提示ＡＨＮＰ大鼠存在肠粘膜损伤，可能与血小板活化因子及血栓素Ａ２介导的肠血流减少有关。     

Oxidative stress. An early phenomenon characteristic of acute experimental pancreatitis.

Acute hemorrhagic pancreatitis was induced in Wistar rats using a retrograde intraductal injection of 5% Na-taurocholate. Rats were sacrificed at 1, 3, 6, and 24 h. Malondialdehyde and sulfhydryl groups concentration, as well as superoxide dismutase and catalase activity were measured in pancreatic, liver, and lung tissue. These parameters, with the exception of catalase, were also determined in serum and peritoneal exudate. Early and profound oxidative stress in each organ was evidenced by marked increases in malondialdehyde concentrations along with marked reductions in levels of sulfhydryl groups and superoxide dismutase; a paradoxical increase in catalase activity, perhaps compensatory, was noted in pancreas and lung. Survival for 24 h was associated with restoration of normality insofar as tissue malondialdehyde concentrations were concerned, but pancreas sulfhydryl groups remained markedly depleted. These data endorse the suggestion that the early provision of such compounds may help to accelerate recovery from hemorrhagic pancreatitis in humans.     

Differential Oxidative Injury in Extrapancreatic Tissues During Experimental Pancreatitis

Oxidative stress is considered to be a pathogenic factor for multisystem organ failure during acute pancreatitis. Infusion of 3% and 5% sodium taurocholate into the pancreatic duct of rats resulted in a 24-hr lethality of 8% and 82%, respectively. Kidney tissue showed a long-lasting significant elevation of malondialdehyde (lipid peroxidation). Only small amounts of this aldehyde were formed in the liver. In the lung malondialdehyde was increased during the first 6 hr after pancreatitis induction. Malondialdehyde levels were not different for pancreatitis initiated by 3% or 5% taurocholate. Protein-bound carbonyls (protein oxidation) in the tissues were not significantly changed at any time point. However, after infusion of 5% taurocholate, lung proteins were oxidatively modified by the product of lipid peroxidation, 4-hydroxynonenal. Another parameter characteristic for pancreatitis with high lethality was the high number of neutrophils in the lungs. We conclude that oxidative stress is important for the injury of extrapancreatic tissues during pancreatitis, but survival is determined by the degree of systemic inflammation.     

Effects of PAF antagonist, BN52021, on the PAF-, methacholine-, and allergen-induced bronchoconstriction in asthmatic children

Platelet-activating factor (PAF) is an inflammatory mediator capable of inducing protracted inflammation of the airways and bronchial hyperreactivity. Twenty-one asthmatic children were evenly divided into three groups and each group performed a double-blind, placebo-controlled and crossover study on the effect of aerosolized BN52021, a PAF antagonist, on the bronchoconstriction induced by PAF, methacholine, or specific allergen, respectively. One group of healthy children was included for comparison. Total WBC, neutrophils, and eosinophils were counted before and after PAF challenge. The results showed the following: (1) six of seven asthmatics and one of seven normal subjects gave a positive bronchial provocation with PAF; (2) in asthmatics, prior inhalation of BN52021 could inhibit the bronchoconstriction induced by PAF (6/6) and allergen (3/7), but not by methacholine; and (3) 5 min after inhalation of PAF, there was a marked decrease of peripheral blood eosinophils and neutrophils that could be inhibited by prior inhalation of BN52021 in normal subjects but not in asthmatics. These findings support the idea that PAF may be involved in the pathogenesis of bronchial asthma and PAF antagonist may have a role in the prevention and treatment of this disease.     

Oxidative stress and lipid peroxidation products:effect of pinealectomy or exogenous melatonin injections on biomarkers of tissue damage during acute pancreatitis

BACKGROUND:Melatonin (N-acetyl-5-methoxytripta-mine) is a free radical scavenger and a strong antioxidant,secreted by the pineal gland.In this study,we evaluated the effects of decreasing and increasing serum melatonin levels on malonyldialdehyde (MDA),superoxide dismutase (SOD),and reduced glutathione (GSH) levels in pancreatic tissue from rats with experimental acute pancreatitis.METHODS:Experimental acute pancreatitis was induced in three groups of Wistar albino rats (10 animals per group) by pancreatic ...     

Excretion of azlocillin and mezlocillin by the normal pancreas and in acute pancreatitis in dogs and rats

Dogs and rats were studied to evaluate the excretion of two new acyl-ureidopenicillins, azlocillin and mezlocillin, in the pancreatic fluid. After intravenous administration of 55 mg X kg-1 of either drug, an extremely low concentration (less than 3.0 micrograms X ml-1) of both antibiotics was measured in pancreatic juice of conscious dogs. In rats, both azlocillin and mezlocillin were excreted by the pancreas in bactericidal concentrations (greater than 10 micrograms X ml-1) during the first 15 min following their injection. In anesthetized dogs and rats in which acute pancreatitis was induced by injection of sodium taurocholate into the main pancreatic duct, the tissue concentration of mezlocillin (55 mg X kg-1 i.v.) was significantly higher than in the pancreatic tissue of control animals. In both instances, bactericidal concentrations of mezlocillin were measured in the pancreatic tissue. During the first 30 min following its injection, the concentration of mezlocillin was about five times higher in inflammed pancreatic tissue than in the normal pancreas (dogs: 44 +/- 14 vs. 5 +/- 3 micrograms X g-1 tissue; rats: 67 +/- 10 vs. 13 +/- 2 micrograms X g-1). These data indicate that (1) azlocillin and mezlocillin are excreted in bactericidal concentrations by the normal pancreas only in rats but not in dogs, and (2) in both species, bactericidal concentrations of mezlocillin can be observed in the normal pancreatic tissue and in acute pancreatitis; its concentration being significantly higher in acute pancreatitis than in controls.     

Involvement of endogenous cholecystokinin in pancreatic regeneration after cerulein-induced acute pancreatitis.

This study was undertaken to determine the involvement of endogenous cholecystokinin (CCK) in the regeneration of pancreatic tissue after cerulein-induced acute pancreatitis treated by the CCK receptor antagonist L364,718. Acute pancreatitis was induced in rats by s.c. injections of cerulein in gelatin (12 micrograms/kg) three times a day for 2 days with controls receiving saline in gelatin. Rats were then divided into four treatment groups: saline-dimethyl sulfoxide (DMSO) (SD), saline-L364,718 (SA), cerulein-pancreatitis-DMSO (CD), and cerulein-pancreatitis-L364,718 (CA). In the first experiment, rats were treated for 3 or 10 days with DMSO or L364,718 (0.1 mg/kg, twice a day). In the second experiment, rats were treated for 13 days with DMSO or L364,718 (1.0 mg/kg, twice a day). After the rats were killed, pancreata were weighed and evaluated for their total protein, amylase, chymotrypsin, RNA, and DNA. We found that destruction of the pancreatic tissue occurred after cerulein-induced pancreatitis and that regeneration of the tissue was in progress but incomplete after 10 days; the low dose of L364,718 did not prevent regeneration. After 13 days, regeneration was still incomplete but the 1-mg dose of L364,718 strongly inhibited spontaneous regeneration. These data suggest that endogenous CCK is an important and potent trophic factor in the regeneration process of pancreatic tissue following an episode of acute pancreatitis.     

Proteasome inhibitor ameliorates severe acute pancreatitis and associated lung injury of rats

AIM： To observe the effect of proteasome inhibitor MG-132 on severe acute pancreatitis （SAP） and associated lung injury of rats. METHODS： Male adult SD rats were randomly divided into SAP group, sham-operation group, and MG-132 treatment group. A model of SAP was established by injection of 5% sodium taurocholate into the biliary- pancreatic duct of rats. The MG-132 group was pretreated with 10 mg/kg MG-132 intraperitoneally （ip） 30 min before the induction of pancreatitis. The changes in serum amylase, myeloperoxidase （MPO） activity of pancreatic and pulmonary tissue were measured. The TNF-α level in pancreatic cytosolic fractions was assayed with an enzyme-linked immunosorbent assay （ELISA） kit. Meanwhile, the pathological changes in both pancreatic and pulmonary tissues were also observed. RESULTS： MG-132 significantly decreased serum amylase, pancreatic weight/body ratio, pancreatic TNF-α level, pancreatic and pulmonary MPO activity （P 〈 0.05）. Histopathological examinations revealed that pancreatic and pulmonary samples from rats pretreated with MG-132 demonstrated milder edema, cellular damage, and inflammatory activity （P 〈 0.05）. CONCLUSION： The proteasome inhibitor MG-132 shows a protective effect on severe acute pancreatitis and associated lung injury of rats.     

Pancreatic regeneration after ethionine-induced acute pancreatitis in rats lacking pancreatic CCK-A receptor gene expression

Background. We examined the effects of cholecystokinin (CCK) on the development of ethionine-induced pancreatitis and pancreatic recovery. We used Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model lacking pancreatic CCK-A receptor gene expression. Methods. Ethionine-induced pancreatitis was induced in the 7-week-old male OLETF rats and in a control group that does not lack the pancreatic CCK-A receptor, Long-Evans Tokushima Otsuka (LETO) rats. The two groups were maintained on a low-protein diet for 11 days. During the last 4 days of the low-protein diet, dl-ethionine 20mg/100g body weight was administered intraperitoneally once daily. Histologic and biochemical examinations of the pancreas were performed, and plasma CCK concentrations were measured on days 1, 4, and 7 after the last ethionine administration. Results. Pancreatic histologic scores for inflammation, hemorrhage, and necrosis in the LETO and OLETF rats were highest on days 1 and 4, respectively. Pancreatic weight, DNA content, and protein level per DNA content in both groups decreased during the low-protein diet, and recovery signs were delayed in the OLETF rats. The highest plasma CCK concentrations in the LETO and OLETF rats were reached on days 1 and 4, respectively. Conclusions. Ethionine-induced pancreatitis developed in the OLETF rats, and their pancreatic regeneration was delayed in comparison to that in the LETO rats. Our results suggested that CCK plays an important role in the development of pancreatitis as well as in the pancreatic repair process.