空肠灌注生大黄对重症急性胰腺炎大鼠的作用

目的探讨生大黄对重症急性胰腺炎(SAP)大鼠血清白细胞介素-6(IL-6)、白细胞介素-8(IL-8)和胰腺组织病理学改变的影响。方法 36只大鼠随机分为正常对照组(假手术组,n=12)、模型组(SAP,n=12)和治疗组(生大黄组,n=12),以5%的牛磺胆酸钠逆行胆胰管注射制备大鼠SAP模型,采用放射免疫法检测大鼠血清IL-6、IL-8浓度。观察胰腺组织湿干重比。光镜下评估胰腺组织病理学积分。结果模型组和治疗组大鼠血清IL-6、IL-8水平明显高于正常对照组,其中治疗组明显低于模型组,P0.01。治疗组胰腺湿干重比及病理组织学评分均显著低于模型组,P0.01。结论生大黄可以使SAP大鼠血清IL-6、IL-8显著降低,并减轻胰腺的病理组织学改变。     

Effect of continuous arterial infusion of protease inhibitor on experimental acute pancreatitis

Journal of Gastroenterology -     

Effect of melatonin on the severity of L-arginine-induced experimental acute pancreatitis in rats

AIM: To determine the effect of melatonin pre- and post-treatment on the severity of L-arginine (L-Arg) -induced experimental pancreatitis in rats. METHODS: Male Wistar rats (25) were divided into five groups. Those in group A received two injections of 3.2 g/kg body weight L-Arg i.p. at an interval of 1 h. In group MA, the rats were treated with 50 mg/kg body weight melatonin i.p. 30 min prior to L-Arg administration. In group AM, the rats received the same dose of melatonin 1 h after L-Arg was given. In group M, a single dose of melatonin was administered as described previously. In group C the control animals received physiological saline injections i.p. All rats were exsanguinated 24 h after the second L-Arg injection. RESULTS: L-Arg administration caused severe necrotizing pancreatitis confirmed by the significant elevations in the serum amylase level, the pancreatic weight/body weight ratio (pw/bw), the pancreatic IL-6 content and the myeloperoxidase activity, relative to the control values. Elevation of the serum amylase level was significantly reduced in rats given melatonin following L-Arg compared to rats injected with L-Arg only. The activities of the pancreatic antioxidant enzymes (Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and catalase (CAT)) were significantly increased 24 h after pancreatitis induction. Mela- tonin given in advance of L-Arg significantly reduced the pancreatic CAT activity relative to that in the rats treated with L-Arg alone. In the liver, L-Arg significantly increased the lipid peroxidation level, and the glutathione peroxi-dase and Cu/Zn-SOD activities, whereas the Mn-SOD activity was reduced as compared to the control rats. Melatonin pre-treatment prevented these changes. CONCLUSION: Melatonin is an antioxidant that is able to counteract some of the L-Arg-induced changes during acute pancreatitis, and may therefore be helpful in the supportive therapy of patients with acute necrotizing pancreatitis.     

Effects of somatostatin on acute canine experimental pancreatitis

Somatostatin is an inhibitory hormone that decreases the secretion and end organ response of cholecystokinin (CCK). Inhibition of hormonal stimulation of pancreatic exocrine secretion by somatostatin may improve the course of acute pancreatitis. Anesthetized dogs underwent cholecystectomy and cannulation of the pancreatic duct, thoracic duct, and portal vein. Twenty experiments were performed in random order with 5 dogs in each group. Hourly measurements of lymph flow and portal and thoracic duct amylase were made. Portal blood insulin, glucagon, and CCK concentrations were determined by radioimmunoassay on samples obtained at the beginning and end of the experiments. Pancreatitis was induced by injecting, under constant pressure, 10 ml bile into the pancreatic duct during 1 min. Somatostatin was administered intravenously (20 micrograms/kg/hr). After 5 h, the dogs were killed, pancreas glands removed and weighed and tissue samples obtained for histologic evaluation. There was a significant increase in lymph amylase output and portal venous amylase and CCK concentrations in the dogs with pancreatitis compared to the control dogs. In dogs with pancreatitis, lymphatic amylase secretion and portal CCK concentrations were significantly decreased by somatostatin. Somatostatin did not significantly alter portal amylase concentrations, pancreas gland weights or histologic inflammation when compared to values from dogs with pancreatitis not treated with somatostatin.     

维拉帕米对实验性急性胰腺炎的保护作用

目的探讨维拉帕米对实验性急性胰腺炎的保护作用．方法雄性Ｗｉｓｔａｒ大鼠２２只，随机分为假手术组（ｎ＝５）、急性胰腺炎组（ｎ＝７）和维拉帕米保护组（ｎ＝１０）．用２０％牛胆酸钠溶液０１ｍｌ／１００ｇ逆行注入大鼠胰管内诱导急性胰腺炎．保护组在实验前经颈静脉输注维拉帕米１０ｍｇ／ｋｇ·ｈ维持１２ｈ．在０，６及１２ｈ分别断尾取血１０ｍｌ，测定血清淀粉酶活性．同时，在光镜和电镜下观察各组胰组织的病理变化．结果急性胰腺炎组在６，１２ｈ的血清淀粉酶值分别为２７９６±４５３和２４７８±３７８（ＩＵ／Ｌ）；其组织水肿和炎症细胞渗出评分分别为３１４±０６９和３００±０５８．维拉帕米保护组在相应时间的血清淀粉酶值仅为２１１３±４１１和１５７９±３１９（ＩＵ／Ｌ）；其组织水肿和炎症细胞渗出评分分别为１００±０８２和０９０±０３２．两组比较，有显著统计学差异（Ｐ＜００５或００１）．同时，前者电镜下见线粒体肿胀，内质网囊池扩大，自噬泡增加，而后者各细胞器基本正常．结论维拉帕米对实验性急性胰腺炎具有保护作用．     

褪黑素干预急性胰腺炎的实验研究进展

褪黑素是一种具有抗氧化作用、免疫调节作用的吲哚类激素,可以下调急性炎症反应过程中炎症介质的表达,减轻急性炎症反应.此文就近年来的褪黑素干预急性胰腺炎的实验研究作一综述.     

Pancreatogastrostomy in experimental acute necrotizing pancreatitis

Experimental acute necrotizing pancreatitis was induced retrogradely in dogs with sunflower oil injected intraductally. Then, a zipper was sutured into the abdominal wound. From the first postoperative day, three different treatments were started: first group: only conservative therapy was used; second group: removal of necrotized tissue and single peritoneal lavage were aplied; and third group: the necrotic part of the pancreas was marsupialized into the stomach. Through the systematic opening of the zipper, the abdominal cavity could easily be explored and the temporal course of disease could be observed in all animals. During this regular procedure, the amylase concentration and the amount of peritoneal exudate were determined. The blood amylase and glucose levels were also measured. On the first postoperative day, the amylase level and the amount of peritoneal exudate were high in all groups. The dogs of the pancreatogastrostomized group showed a dramatic decrease of the exudate and the most advantageous temporal course of the blood amylase level. The survival rate similarly was advantageous in the pancreatogastrostomized group.     

Effect of new oligopeptide inhibitors of elastase on acute experimental pancreatitis in the rat

Acute experimental pancreatitis was induced in male Wistar rats by retrograde injection of 0.4 ml 2% sodium taurocholate into the common choledochopancreatic duct. Prophylactic intraperitoneal injection of 20 mg glutaryl-trialanine-ethylamide, Glt-(Ala)3-NH-Et, 30 min. before induction of pancreatitis reduced the amount of fat necroses and the activity of amylase and lipase in ascites. Repeated intraperitoneal injection of this inhibitor decreased pancreatic hemorrhage. Simultaneous administration of 20 mg Glt-(Ala)3-NH-Et intraperitoneally, and 10 000 KIU of aprotinin intravenously was followed by the most extensive inhibitory effect. Prophylactic and repeated administration of both inhibitors also reduced the area of pancreatic hemorrhage. The same mode of administration of 20 mg undecenoyl-aspartyl-dialanyl-proline-ethylamide, UDE-Asp-(Ala)2-Pro-NH-Et, intraperitoneally and 20 000 KIU of aprotinin intramuscularly, resulted in selective inhibition of fat necroses in all localizations. Glt-(Ala)3-NH-Et and UDE-Asp-(Ala)2-Pro-NH-Et are considered effective inhibitors of various macroscopic and biochemical signs of acute pancreatitis in the rat during short-ferm experiments, if administered prophylactically or early after induction of the disease.     

Effect of microcirculatory perfusion on distribution of trypsinogen activation peptides in acute experimental pancreatitis

Extraintestinal trypsinogen activation peptides (TAP) have been shown to correlate with severity of acute pancreatitis in humans as well as in various animal models. Ischemia superimposed on experimental pancreatitis, however, increases acinar cell injury without increasing TAP in plasma. We speculated that TAP generated in the pancreas might not reach the circulation in necrotizing pancreatitis due to decreased pancreatic perfusion. To test the hypothesis that generation of TAP in plasma is related to pancreatic perfusion and that plasma TAP may therefore underestimate acinar cell injury in necrotizing disease, we correlated TAP in pancreatic tissue and body fluids with capillary pancreatic blood flow in necrotizing and edematous pancreatitis. The ratio between necrosis and TAP in tissue was similar in both models; the ratio between TAP in plasma and tissue, however, was significantly lower in necrotizing pancreatitis, indicating that a certain amount of TAP generated in the pancreas did not reach the circulation. Decreased pancreatic perfusion found in necrotizing pancreatitis was consistent with this finding. Our data suggest that TAP in tissue is most reliable to indicate severity of acute pancreatitis, whereas plasma TAP may underestimate pancreatic injury in necrotizing disease due to decreased pancreatic perfusion.     

早期阻断MCP-1对实验性急性坏死性胰腺炎的作用

目的 探讨趋化因子MCP-1对实验性急性坏死性胰腺炎(ANP)及其并发症的影响.方法 60只SD大鼠按数字表法分为假手术组、ANP组和MCP-1多抗干预组(干预组),各20只.采用3.5%牛黄胆酸钠制备ANP模型,干预组于制模后0、6 h皮下注射抗MCP-1多抗.观察血清淀粉酶、MCP-1、D-乳酸含量变化;观察胰腺、肺、小肠组织病理改变及MCP-1 mRNA的表达;检测胰腺MCP-1蛋白表达;检测肺、小肠髓过氧化酶(MPO)含量.结果 干预组12 h的血淀粉酶、MCP-1、D-乳酸含量分别为(4666±412)U/L、(39.53±8.25)pg/ml和(6.3±2.2)mg/L,均显著低于ANP组的(9611±363)U/L、(63.42±9.32)pg/ml和(9.3±2.1)mg/L(P值均<0.05);胰腺、肺、小肠组织MCP-1 mRNA表达量分别为0.431±0.009、0.211±0.018和0.442±0.017,均显著低于ANP组的0.624±0.010、0.523±0.019和0.569±0.024(P值均<0.05);胰腺MCP-1蛋白表达评分为2.0±0.1,显著低于ANP组的4.0±0.2(P<0.05);肺、小肠组织MPO含量分别为(11.1±3.0)U/g组织和(19.2±2.0)U/g组织,均与ANP组的(39.2±3.1)U/g组织和(13.1±2.1)U/g组织有显著差异(P值均<0.05).结论 早期阻断MCP-1不但可以减轻急性胰腺炎病理损伤,而且能减轻急性肺损伤和肠屏障的损伤程度.     

Effect of endotoxin administration on the severity of acute pancreatitis in two experimental models

Summary Conclusions Endotoxemia can transform acute pancreatitis (AP) into a more severe form of the disease in models of AP provoked by common pancreatico-biliary duct ligation orl-arginine injection. Background It has been shown that systemic endotoxemia is a common feature in severe AP. The effect of endotoxemia on the course of experimental pancreatitis is unknown. Methods AP was induced by common pancreatico-biliary duct ligation (experiment 1) and ip injection of 250 mg/100 g body wt ofl-arginine (experiment 2). Test animals of both experiments received ip injections of 0.5 and 1.0 mg/100 g body wt of endotoxin at the induction of AP. Saline-treated and only endotoxin-dosed animals served as controls for both experiments. Mortality rates and pancreatic histology were investigated at 48 h. Results The mortality rate was significantly elevated (60%,p<0.05) in experiment 1 when 1.0 mg/100 g of endotoxin was given. In experiment 2, the mortality rate was also increased (30%) at this dose of endotoxin without reaching significance. Histologic changes were more severe in both groups of AP treated by the two doses of endotoxin than without it. Acinar necrosis and hemorrhage were highly elevated (p<0.01) in both experiments when AP was combined with 1.0 mg/100 g body wt of endotoxin. The animals receiving only endotoxin showed only slight inflammatory and necrotic changes.     

酪酪肽对实验性急性胰腺炎的治疗作用

目的探讨酪酪肽(Peptide YY,PYY)对实验性急性胰腺炎大鼠(AP)的治疗效果,并对其机制进行探讨。方法取40只SD大鼠,雌雄不限,随机分为胰腺炎组(n=20)和酪酪肽治疗组(n=20),急性胰腺炎模型采用经腹腔注射精氨酸完成,测定48 h后大鼠血清及胰腺组织匀浆中的丙二醛(MDA)含量,血清中肿瘤坏死因子-α含量,光镜下观察胰腺组织的病理变化。结果 PYY能有效减轻AP大鼠胰腺的病理损伤,与胰腺炎组相比,PYY组血清中及胰腺组织匀浆中的MDA含量下降,血清中肿瘤坏死因子-α的含量下降。结论 PYY可能通过抗氧自由基的生成,减轻组织的过氧化损伤,以及通过抑制某些细胞因子的作用而对急性胰腺炎发挥保护作用。     

Protective effects of rhubarb on experimental severe acute pancreatitis

AIM: To investigate the effects of rhubarb on severe acute pancreatitis (SAP) in rats. METHODS: Severe acute pancreatitis was induced by two intraperitoneal injections of cerulein (40 μg/kg body weight) plus 5-h restraint water-immersion stress. Rhubarb (75-150 mg/kg) was orally fed before the first cerulein injection. The degree of pancreatic edema, serum amylase level, local pancreatic blood flow (PBF), and histological alterations were investigated. The effects of rhubarb on pancreatic exocrine secretion in this model were evaluated by comparing with those of somatostatin. RESULTS: In the Cerulein+Stress group, severe edema and diffuse hemorrhage in the pancreas were observed, the pancreatic wet weight (11.60&#177;0.61 g/Kg) and serum amylase (458 490&#177;43 100 U/L) were markedly increased (P&lt;0.01 vs control). In the rhubarb (150 mg/kg) treated rats, necrosis and polymorphonuclear neutrophil (PMN) infiltration in the pancreas were significantly reduced (P&lt;0.01), and a marked decrease (50%) in serum amylase levels was also observed (P&lt;0.01). PBF dropped to 38% (93&#177;5 mL/min per 100 g) of the control in the Cerulein+Stress group and partly recovered in the Cerulein+Stress+Rhubarb 150 mg group (135&#177;12 mL/min per 100 g) (P&lt;0.01). The pancreatic exocrine function was impaired in the SAP rats. The amylase levels of pancreatic juice were reduced in the rats treated with rhubarb or somatostatin, comparing with that of untreated SAP group. The bicarbonate concentration of pancreatic juice was markedly elevated only in the rhubarbtreated group (P&lt;0.01). CONCLUSION: Rhubarb can exert protective effects on SAP, probably by inhibiting the inflammation of pancreas, improving pancreatic microcirculation, and altering exocrine secretion.     

还原型谷胱甘肽对实验性急性坏死性胰腺炎的治疗效果及机制

目的 探讨还原型谷胱甘肽(GSH)对实验性ANP的疗效及其机制.方法 54只雄性Sprague-Dawley大鼠随机分为对照组(NS)、ANP组、GSH干预组(GSH组)3组,每组再分成3 h、6 h和12 h 3组.经胆胰管内注射3.5%牛磺胆酸钠0.1 ml/100 g体重制备ANP模型.GSH组在制模后即刻腹腔注射GSH 12.5 mg/100 g体重.检测各组不同时间点血淀粉酶、超氧化物歧化酶(SOD)及丙二醛(MDA)含量,并取胰腺组织常规病理检查,RT-PCR法和免疫组织化学法检测胰腺组织中NF-κB p65 mRNA及蛋白表达.结果 GSH 3 h、6 h组胰腺组织病理分值、血清淀粉酶、MDA含量、NF-κB p65 mRNA及蛋白表达较同时点ANP组明显减弱(P＜0.05);血清SOD明显增加(P＜0.05).结论 GSH腹腔注射后短期内能够改善ANP大鼠的胰腺组织损害,其机制可能通过抗氧自由基及抑制胰腺组织NF-κB的表达而发挥作用.