急性水肿性胰腺炎大鼠胰腺微血流变化和环氧合酶-2的表达

目的　探讨环氧合酶 2 (COX 2 )mRNA的表达在急性水肿性胰腺炎 (AEP)大鼠胰腺局部微血管变化中的作用。方法　皮下注射蛙皮缩胆囊肽 (Caerulein)诱发急性水肿性胰腺炎。RT PCR检测胰腺COX 2mRNA表达。分光光度法检测胰腺炎指标 :血浆髓过氧化酶 (MPO)和血清淀粉酶 (AMS)的活性。异硫氰酸荧光素标记红细胞 (FITC RBC)技术对胰腺活体进行局部微血管观察。结果　COX 2mRNA在正常对照组各时点均呈低水平表达 ,而在AEP组表达在Caerulein诱发后上调 ;与正常组相比 ,AEP组血清淀粉酶 (AMS)、血浆髓过氧化酶 (MPO)活性水平增加 (P <0 0 5 ) ;与对照组相比 ,AEP组的胰腺微血管改变如下 :胰腺毛细血管血流 4～ 8h减少、功能毛细血管密度 4～ 8h减少、毛细血管在 8h趋于通透。结论　COX 2在AEP组中的表达上调是客观反映胰腺微循环功能损害 ,如毛细血管灌流、血流及组织水肿等的指标。     

犬急性水肿型胰腺炎胰液外引流模型的制备及胰腺外分泌功能的观察

目的建立犬急性水肿型胰腺炎胰液外引流模型,观察胰腺外分泌的功能。方法健康杂种犬12只,分为对照组和胰腺炎组,每组6只。制备犬胰液外引流模型后24h,5%牛磺胆酸钠(0.5mL/kg)1mL/min胰管逆行注射制备急性水肿型胰腺炎模型。每12h收集胰液一次,测定胰液的分泌量,胰液中淀粉酶、脂肪酶、总蛋白、pH值和主要电解质含量。制模后在不同时段采血,检测血中的淀粉酶、脂肪酶的浓度。取胰腺组织行病理学检查。结果成功建立犬急性水肿型胰腺炎胰液外引流模型。胰腺炎组胰液分泌量,胰液中淀粉酶、脂肪酶、总蛋白、HCO3-含量和pH值低于对照组(P0.05),Cl-高于对照组(P0.05)。胰液中的Na~+、K~+、Ca~(2+)、Mg~(2+)胰腺炎组与对照组差异无统计学意义(P0.05)。结论本模型适用于急性水肿型胰腺炎胰腺外分泌功能的研究。     

Phosphate depletion impairs insulin secretion by pancreatic islets.

Phosphate depletion (PD) is associated with resistance to the peripheral action of insulin and with glucose intolerance. However, data on the effect of PD on insulin secretion are not consistent, and were derived indirectly by measurements of blood levels of insulin during intravenous glucose tolerance test (IVGTT) or with hyperglycemic clamp technique. Direct evidence for an effect of PD on insulin secretion by pancreatic islets is not available, and the potential mechanisms through which PD may affect insulin secretion are not known. We performed IVGTT, examined in vitro insulin secretion by pancreatic islets, and evaluated various factors involved in insulin secretion in PD and pair weighed (PW) rats. PD animals had fasting hyperglycemia and normal plasma insulin levels, and displayed abnormal IVGTT as compared to PW rats. Both initial and late phases of D-glucose-induced insulin secretion from islets were markedly and significantly (P less than 0.01) lower than from islets of PW rats. In contrast, D-glyceraldehyde-induced insulin release in PD rats was similar to that of PW rats. [H3]2-deoxyglucose uptake by islets and their cyclic AMP content after exposure to D-glucose, D-glyceraldehyde or forskolin were not different among the two groups of animals. Insulin content in PD islets was modestly but significantly (P less than 0.01) higher than PW islets. In PD islets, ATP content and the ATP/ADP ratio at basal state and after incubation with 16.7 mM D-glucose were significantly (P less than 0.01) lower and resting cytosolic calcium was significantly (P less than 0.01) higher than in PW islets.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute hemorrhagic pancreatitis in the dog. 5. The effect of antidiuretic hormone on pancreatic exocrine secretion

Acute hemorrhagic pancreatitis was created in dogs using the closed duodenal loop technique. After 18 hours, a a constant rate of pancreatic exocrine secretion was stimulated with secretin. A direct relationship was observed between the percentage inhibition of secretin-stimulated pancreatic exocrine flow and the dose of antidiuretic hormone administered to dogs with acute hemorrhagic pancreatitis. The acute hemorrhagic pancreatitis reduced the sensitivity of the exocrine pancreas to secretin and antidiuretic hormone.     

Acute pancreatitis and pancreatic fistula formation

The cause, management and outcome of 23 patients with a pancreatic fistula following acute pancreatitis are reviewed. Nineteen patients developed an external fistula following necrosectomy or drainage of a pancreatic abscess or pseudocyst; four of these patients died. In the 15 survivors spontaneous closure occurred in 11 cases with low output fistulae; operative intervention was needed in the four cases with high output fistulae. Four patients with internal fistulae had not undergone previous surgery; two of them had a pancreaticopleural fistula with associated pancreaticogastric fistulae, while two had pancreatic ascites. All four of these patients required surgical intervention and one died.     

Acute pancreatitis after experimental pancreatic transplantation

We describe our serendipitous finding of a transplantation model of hemorrhagic pancreatic necrosis. The slow evolution, from edematous interstitial pancreatitis to hemorrhagic necrosis over the course of 8 days made the model amenable to therapeutic manipulation. The possible pathogenesis is discussed with reference to the published literature. From comparisons between the histologic and biochemical features of isografts and allografts, we suggest that ischemia-reperfusion injury initiates pancreatitis through oxygen-free radicals, and that the transformation to hemorrhagic pancreatic necrosis in allografts reflects the involvement of chemotactic immune factors and extracellular secretions from activated proteases.     

中药复方“清下1号”对急性水肿性胰腺炎局部微循环损伤的作用

目的探讨大鼠急性水肿性胰腺炎(AEP)动物模型的早期微循环改变及中药复方清下1号（MCP-1）对AEP胰腺微循环的作用。方法用异硫氰酸荧光素-荧光标记红细胞(FITC-RBC)胰腺活体微循环技术、微血管树脂/墨汁灌注光镜和扫描电镜、透射电镜技术,用蛙皮缩胆囊肽诱发大鼠急性胰腺炎（AP）动物模型,观察36只Wistar大鼠的早期微循环改变、MCP-1应用后胰腺局部微循环的反应。结果与AEP自然病程组比较,MCP-1治疗组血清淀粉酶由（2997.7±801.4）?IU/L降至（1909.7±295.5）?IU/L（P<0.01）;胰腺间质炎性细胞浸润减少;腺泡细胞胞浆内空泡减少;毛细血管密度由（52.8±6.1）%增至（63.2±5.5）%（P<0.01);微血管管径由（4.5±0.4）?μm增至（5.9±0.6）?μm（P<0.05）;FITC-RBC显示胰腺微循环流速、流量增加,灌流稳定(0.87±0.06)nl/min（P<0.01)。结论MCP-1具有显著改善AP胰腺微循环的作用,抗AP胰腺局部微循环损伤是实现MCP-1疗效的重要机制。     

左旋精氨酸对急性胰腺炎的作用

探讨左旋精氨酸（Ｌ－Ａｒｇ）在大鼠急性水肿性胰腺炎（ＡＥＰ）中的作用。方法观察倍数剂量Ｌ－Ａｒｇ治疗ＡＥＰ大鼠后,血浆和胰组织一氧化氮（ＮＯ）浓度、血浆淀粉酶、平均动脉压（ＭＡＰ）、胰组织病理的变化。结果ＡＥＰ大鼠血浆、胰组织ＮＯ浓度明显降低,Ｌ－Ａｒｇ５０、１００ｍｇ／ｋｇ升高血浆、胰组织ＮＯ浓度,改善了大鼠ＡＥＰ;Ｌ－Ａｒｇ８００、１６００ｍｇ／ｋｇ体重使ＮＯ浓度过度升高,加重ＡＥＰ成为急性出血坏死性胰腺炎（ＡＨＮＰ）;胰组织病理评分与血浆、胰组织ＮＯ浓度呈正相关。Ｌ－Ａｒｇ对ＭＡＰ的影响较小。血浆淀粉酶除８００ｍｇ／ｋｇ体重组明显降低外,其余各组间无明显差异。结论Ｌ－Ａｒｇ因升高ＮＯ浓度而参与了大鼠ＡＥＰ的病理过程。     

碱性成纤维细胞生长因子对大鼠急性水肿性胰腺炎的治疗作用

目的　观察外源性碱性成纤维细胞生长因子(bFGF)对急性水肿性胰腺炎大鼠的治疗作用,并探讨其作用机制。方法　予雄性SD大鼠间隔1h皮下注射蛙皮素5 .5 μg/kg体重和7.5μg/kg体重诱导急性水肿性胰腺炎,3h后腹腔内注射bFGF 10 0 μg/kg体重。观察各组大鼠胰腺炎生化及病理学等指标的变化。结果　bFGF治疗组大鼠的血清淀粉酶,脂肪酶以及胰腺组织湿/干质量比率(13 83 .0±94.6)、(194.0±43 .6)和(4 .3 2±0 .3 2 )U /L明显低于非治疗组(P <0 .0 1) ,而与空白对照组差异无统计学意义(P >0 .0 5 )。光镜下显示其胰腺组织炎症表现显著改善。免疫组织化学结果显示该组胰腺腺泡细胞被5 溴 2 去氧胞苷标记的细胞核数[(18.9±1.4)个/显微镜视野,n =10 ]明显多于非治疗组(P <0 .0 1)。结论　早期外源性bFGF对蛙皮素诱导的大鼠急性水肿性胰腺炎有显著的治疗作用,其作用机制是通过减轻胰腺炎症和促进胰腺组织再生来实现的     

Dimephosphon in complex therapy of acute edematous pancreatitis

Clinical investigations of 120 patients have shown that Dimephosphon included in complex treatment of acute edematous pancreatitis facilitates more rapid arrest of the symptoms. An important effect of the drug is its ability to decrease the level of endogenous intoxication by both the hydrophilic and hydrophobic components. It was established that one of the mechanisms of favorable action of the drug is its ability to inhibit LPO, to decrease activity of phospholipase A2. The drug possessing the cytoprotecting effect promotes rapid restoration of the functional state of the liver, in particular its detoxicating, albumin synthesizing ability that is not least of the factors of optimization of the complex therapy.     

A defect late in stimulus-secretion coupling impairs insulin secretion in Goto-Kakizaki diabetic rats.

A widely accepted genetically determined rodent model for human type 2 diabetes is the Goto-Kakizaki (GK) rat; however, the lesion(s) in the pancreatic islets of these rats has not been identified. Herein, intact islets from GK rats (aged 8-14 weeks) were studied, both immediately after isolation and after 18 h in tissue culture. Despite intact contents of insulin and protein, GK islets had markedly deficient insulin release in response to glucose, as well as to pure mitochondrial fuels or a non-nutrient membrane-depolarizing stimulus (40 mmol/l K+). In contrast, mastoparan (which activates GTP-binding proteins [GBPs]) completely circumvented any secretory defect. Basal and stimulated levels of adenine and guanine nucleotides, the activation of phospholipase C by Ca2+ or glucose, the secretory response to pertussis toxin, and the activation of selected low-molecular weight GBPs were not impaired. Defects were found, however, in the autophosphorylation and catalytic activity of cytosolic nucleoside diphosphokinase (NDPK), which may provide compartmentalized GTP pools to activate G-proteins; a deficient content of phosphoinositides was also detected. These studies identify novel, heretofore unappreciated, defects late in signal transduction in the islets of our colony of GK rats, possibly occurring at the site of activation by NDPK of a mastoparan-sensitive G-protein-dependent step in exocytosis.     

急性水肿性胰腺炎血管内皮细胞血管内皮钙粘着蛋白的表达及中药对其的影响

目的　了解急性水肿性胰腺炎 (AEP)胰腺外分泌部血管内皮细胞血管内皮钙粘着蛋白 (VE cadherin)的表达、分布及中药对它的调节作用。方法　应用荧光免疫组织化学染色和共聚焦激光扫描显微镜技术 ,观察 2 6只正常、AEP及中药华西胰腺炎 1号 (WPY)治疗的AEPWistar大鼠胰腺血管内皮VE cadherin的表达。结果　在AEP病程中 ,VE cadherin在微血管内皮细胞间连接处消失 ,毛细血管内皮处分布异常 ,其表达 ( 1.14± 0 .0 8、0 .90± 0 .0 8、1.19± 0 .0 6、1.0 4± 0 .0 5 )较正常 ( 1.41± 0 .0 6 )减少 ,两者比较 ,差异有非常显著性 (P <0 .0 1)。治疗后 ,定位及其表达( 1.2 5± 0 .0 7,P <0 .0 1)有所恢复。结论　VE cadherin分布异常、表达水平下降是AEP血管通透性增高的重要原因。中药WPY可改善其表达。     

Effect of aging on pancreatic secretion in rats

We have characterized the effects of aging on the pancreatic exocrine secretory response to the normal stimulatory hormones, secretin, and cholecystokinin. Young (6 month old) and aged (26 months old) male Sprague-Dawley rats were prepared with pancreatic fistulas and challenged with different doses of secretin (0.03, 0.06, and 0.12 nmol/kg) and cholecystokinin-8 (0.3, 0.6, and 1.2 nmol/kg) intravenously. The pancreatic secretion was measured for volume and bicarbonate and protein outputs. Our results show that in aged rats, the basal pancreatic secretion volume and protein and bicarbonate outputs were significantly reduced, and the pancreatic secretion volume and protein and bicarbonate responses to graded doses of secretin or cholecystokinin-8 were significantly reduced. This study demonstrates that pancreatic exocrine function in rats diminishes with age.     

Acute haemorrhage associated with pancreatic pseudocyst and chronic pancreatitis

The present study reports 18 patients operated on for chronic pancreatitis complicated by bleeding in the upper gastrointestinal tract, the peritoneal cavity or the retroperitoneal space. Damage to the splenic artery by a pancreatic pseudocyst was the most common reason for the bleeding (10 patients, 56%) and the most common site was the duodenum (10 patients, 56%). Eleven patients were treated by transcystic multiple suture ligations combined with external drainage of the pseudocyst, and seven by pancreatic resection or total pancreatectomy. Hospital mortality was 33% (6 patients); two patients had undergone transcystic suture ligation, and four pancreatic resection. Five patients needed a reoperation because of further bleeding, four of them having been treated initially by transcystic suture ligation. Our results suggest that haemostasis by suture ligation is a method to be recommended if the patient's condition has been exacerbated by severe haemorrhage.     

Acute hypercalcemia, pancreatic duct permeability, and pancreatitis in cats

We investigated the effects of hypercalcemia on pancreatic duct permeability and pancreatitis in cats. Acute hypercalcemia was maintained by an infusion of calcium gluconate; controls received saline solution. Chronic hypercalcemia was maintained by diet and by vitamin D and dihydrotachysterol injections. Portal venous blood was analyzed for large dextran molecules that had been perfused through the pancreatic duct. In a separate group of hypercalcemic animals, we perfused the duct with activated pancreatic enzymes to induce acute pancreatitis. After 24 hours of hypercalcemia, dextrans were detected in the portal venous blood of 6 of 11 hypercalcemic and none of the 6 control animals (p less than 0.05). After 12 hours of hypercalcemia, dextrans were detected in all 7 hypercalcemic and 1 of 7 control animals (p less than 0.001). The degree of pancreatic inflammation was greater in the 12-hour animals than in the controls (p less than 0.001). After 14 days of hypercalcemia, however, there were no differences in dextran permeability or pancreatitis in experimental or control animals. Our results indicate that acute hypercalcemia increases the permeability of the pancreatic duct to molecules the size of pancreatic enzymes. This could be important in the pathogenesis of acute pancreatitis associated with hypercalcemic states.     

Acute pancreatitis in Hong Kong.

A series of 311 Chinese patients with acute pancreatitis admitted to Queen Mary Hospital, Hong Kong, over a 10-year period is reviewed. Biliary tract disease was associated with pancreatitis in 52.4 per cent of patients and 77.9 per cent of them had stones, mud or parasites in the common bile duct. Fever and jaundice were present in 55 per cent and 41.2 per cent of patients respectively. Because of the prevalence of recurrent pyogenic cholangitis among the indigenous population, emergency operation, with the aim of common duct decompression, was conducted in 54.3 per cent of patients during the acute episode, with a mortality rate of 14.8 per cent. Five of 142 patients (3.5 per cent) died whilst on conservative treatment and all 5 had haemorrhagic pancreatitis. The overall mortality rate was 9.6 per cent. Exploration of the common bile duct, which was carried out in 57.4 per cent of patients in the acute phase, was not associated with a higher mortality than when laparotomy alone was performed, and 19 patients had sphincteroplasty without any death. Subtotal pancreatectomy was performed in 2 patients with haemorrhagic pancreatitis with 1 death.     

Acute gallstone pancreatitis in childhood.

Acute pancreatitis is rarely considered in the diagnosis of paediatric abdominal pain and can be misdiagnosed. Gallstones are uncommon in children and are a rare cause of pancreatitis. Trauma, infections and idiopathic causes are the commonest aetiological factors. Three cases of gallstone-induced acute pancreatitis with jaundice in children are reported which resolved with conservative treatment. The gallstones were managed by laparoscopic cholecystectomy with or without endoscopic retrograde cholangiopancreatography (ERCP). The three children had presented previously to a doctor with symptoms of gallstone disease but the diagnosis was missed. It is concluded that acute pancreatitis should be considered in children presenting as an emergency with abdominal pain. Children with recurrent attacks of upper abdominal pain should be investigated for gallstone disease so that the diagnosis is made before the development of potentially serious complications such as acute pancreatitis and jaundice.