实验研究细胞因子在急性胰腺炎发病机理中的作用

目的：观察大鼠血清中细胞因子在急性胰腺炎发病机理中的作用。方法：检测血清中细胞因子和TNF-α，观察胰、肝、肺、肾的病理变化及胰腺细胞培养液中淀粉酶和PLA_2化。结果：在坏死性胰腺炎和水肿性胰腺炎大鼠血清中，IL-1β、IL-6、IL-2和TNF-α都明显高于正常对照组(P＜0.01），水肿性和坏死性胰腺炎的胰组织中4种细胞因子都高于正常胰腺组（P＜0.01），但两者之间未见明显差别。水肿性胰腺炎分离培养的胰腺细胞上清液中测出IL-6和TNF-α都高于正常胰腺组。结论:急性胰腺炎症过程中有多种细胞因子参与发病机理，其在体内放大作用造成胰腺本身在内的全身多器官功能损害，而且细胞因子的升高与疾病的严重程度相关。     

实验研究细胞因子在急性胰腺炎发病机理中的作用

目的：观察大鼠血清中细胞因子在急性胰腺炎发病机理中的作用。方法：检测血清中细胞因子和TNF-α，观察胰、肝、肺、肾的病理变化及胰腺细胞培养液中淀粉酶和PLA2变化。结果：在坏死性胰腺炎和水肿性胰腺炎大鼠血清中，IL-1β、IL-6、IL-2和TNF-α都明显高于正常对照组(P<0．01)，水肿性和坏死性胰腺炎的胰组织中4种细胞日子都高于正常胰腺组(P<0．01)，但两者之间未见明显差别：水肿性胰腺炎分离培养的胰腺细胞上清液中测出IL-6和TNF-α都高于正常胰腺组。结论：急性胰腺炎症过程中有多种细胞因子参与发病机理，其在体内放大作用造成胰腺本身在内的全身多器官功能损害，而且细胞因子的升高与疾病的严重程度相关。     

胰腺微循环障碍与急性胰腺炎

急性坏死性胰腺炎（ＡＮＰ）以其高病死率而成为临床医学的一大难题，其发病机理至今尚不十分清楚。１００多年的临床和实验研究表明，传统的“自身消化学说”已不能满意地解释急性胰腺炎（ＡＰ）复杂的病理过程和不断加剧的临床现象。有大量依据证实，在ＡＰ的病理过程中，突出地存在以缺血为特征的胰腺微循环障碍。９０年代以来，有关ＡＰ与胰腺微循环关系的研究逐渐增多，对胰腺微循环紊乱在ＡＰ发病机理中的作用也有了更深层次的认识：胰腺微循环紊乱在ＡＰ的发病机理中是动因还是结果取决于ＡＰ的临床及病理类型、动物模型的选择、给药…     

急性胰腺炎的CT评价

目的：探讨急性胰腺炎及其并发症的CT表现和急性胰腺炎严重程度的评价方法。方法：回顾CT诊断急性胰腺炎及其并发症、评价急性胰腺炎严重程度的文献。结果：CT增强扫描早期判断胰腺坏死的检测率为90％，而对发病4d后评价胰腺坏死的敏感性几乎为100％，急性胰腺炎CT严重度指数与胰腺局部并发症的发生和急性胰腺炎死亡率有极好的相关性。结论：CT增强扫描能显示胰腺坏死、评价炎性过程的范围和发现局部并发症，是综合评价急性胰腺炎的首选影像学方法。     

胰腺微循环障碍与急性坏死性胰腺炎

急性坏死性胰腺炎（ANP）的发病机理至今不清。近年，器官微循环实验新技术的应用，使ANP胰腺微循环改变的研究取得长足进展，从一个侧面揭示了胰腺局部微循环障碍在ANP发病机理中的作用，同时也带给临床治疗以若干启示。     

胰腺微循环障碍与急性坏死性胰腺炎

急性坏死胰腺炎（ＡＮＰ）的发病机理至今不清，近年，器官微循环实验新技术的应用，使ＡＮＰ胰腺微循环改变的研究取得长足进展，从一个侧面揭示了胰腺局部微循环障碍在ＡＮＰ发病机理中的作用，同时也带给临床治疗以若干启示。     

NLRP3炎性小体与急性胰腺炎的研究进展

目的探讨NLRP3炎性小体与急性胰腺炎病情的发展,以及与急性胰腺炎导致的胰腺原位和胰腺外损伤的关系。方法对近年来国内外有关NLRP3炎性小体与急性胰腺炎病情发展,胰腺原位和胰腺外脏器损伤研究的相关文献进行综述。结果急性胰腺炎发生时,NLRP3炎性小体激活参与了急性胰腺炎时各脏器的损伤,NLRP3炎性小体激活越多,对机体的损伤越严重,通过对NLRP3炎性小体激活机制的调节,可以减少NLRP3炎性小体的激活,并最终减轻各脏器的损伤。结论 NLRP3炎性小体的激活参与了急性胰腺炎的进程,但仍需进一步临床研究予以验证。     

胰腺高分泌刺激而非胰管梗阻可增加酒精性胰腺损伤(英)

在酒精性胰腺炎的发病机理中，酒精如何引起胰腺炎的发作和胰腺对酒精敏感的前提条件目前仍不请楚。一般认为是酒精毒性和多种因素的综合作用，如酒精引起的胰腺外分泌刺激伴有Oddi括约肌的激惹（水肿或痉挛）。本文作者经研究发现急性酒精性胰腺炎的发病要有外分泌高刺激的存在，这也许是CCK的作用，但不支持Oddi括约肌引起的梗阻在其中的作用。     

肿瘤坏死因子在急性胰腺炎并发肠粘膜屏障损害中的作用

目的 了解炎性细胞因子在急性胰腺炎发病机理及其并发器官功能障碍中的作用。方法 采用文献回顾方法对大量有关急性胰腺炎、细胞因子、临床资料和动物实验的有关文献进行综述。结果 急性胰腺炎时肿瘤坏死因子ＴＮＦ－α（ｔｕｍｏｒ ｎｅｃｒｏｓｉｓ ｆａｃｔｏｒ－α）和其他细胞因子水平明显升高,胰腺和肠道是主要的产生场所。它们的产生与动物模型的不同无关,抗细胞因子疗法可降低它们的水平。结论 炎性细胞因子在急性胰     

胰腺假性囊肿治疗的研究进展

正胰腺假性囊肿(pancreatic pseudocyst,PPC)是急慢性胰腺炎或胰腺外伤后较为常见的并发症,胰腺手术后也偶有发生。2012年亚特兰大急性胰腺炎国际共识曾阐释其发病机理:PPC是胰腺主胰管或其分支破坏引起的,后续的胰液渗漏导致持续的胰周液体聚集,并且积液被轮廓分明的炎性囊壁所包裹,而外围囊壁并无上皮细胞,其囊腔内基本无可辨识的固体成分~([1])。典型病例一般发生在急性胰腺炎4周后,发生率为5%～15%,其中以酒精相关     

Classification and pathogenesis of pancreatitis

Full functional and morphologic restitution of the pancreas is possible after an attack of acute pancreatitis if the initiating agent or process is removed, whereas chronic pancreatitis is associated with irreversible changes. Most attacks of acute pancreatitis are related to biliary tract stone disease, and it is likely that the offending stone causes obstruction of the pancreatic duct with ductal hypertension. Some recent experimental observations suggest that acute pancreatitis may involve intra-acinar cell activation of digestive enzymes by lysosomal hydrolases. Most patients with chronic pancreatitis develop their disease after many years of ethanol abuse, but the events underlying the pathogenesis of chronic pancreatitis are not known.     

JPN Guidelines for the management of acute pancreatitis: treatment of gallstone-induced acute pancreatitis

Gallstones, along with alcohol, are one of the primary etiological factors of acute pancreatitis, and knowledge of the etiology as well as the diagnosis and management of gallstones, is crucial for managing acute pancreatitis. Because of this, evidence regarding the management of gallstone-induced pancreatitis in Japan was collected, and recommendation levels were established by comparing current clinical practices with optimal clinical practices. The JPN Guidelines for managing gallstone-induced acute pancreatitis recommend two procedures: (1) an urgent endoscopic procedure should be performed in patients in whom biliary duct obstruction is suspected and in patients complicated by cholangitis (Recommendation A); and (2) after the attack of gallstone pancreatitis has subsided, a laparoscopic cholecystectomy should be performed during the same hospital stay (Recommendation B).     

残余胆囊结石与急性胰腺炎8例分析

目的 探讨残余胆囊结石与急性胰腺炎发作的关系及其外科治疗方法.方法 回顾性分析1998年6月-2007年12月期间收治的13例残余胆囊结石患者的临床资料,就其中8例残余胆囊结石与急性胰腺炎作相关分析.13例患者均于2～9年前行过胆囊切除手术,术后首次出现症状的时间为1个月～8年.均行B超、CT、磁共振胰胆管造影(MRCP)检查等诊断为残余胆囊.结果 术后证实其中2例为泥沙样色素结石;6例为胆固醇结石(0.2～0.5 cm,平均3.2 cm);1例合并胰胆管合流异常(anomalous pancreaticobiliar ductal union,APBDU);5例无异常发现;8例(61.5%)合并急性胰腺炎发作史.患者均行残余胆囊切除术,行胆总管囊肿切除和胆肠Roux-en-Y内引流1例,胆总管切开取石T管引流3例.术后随访8例残余胆囊结石,6例无胰腺炎发作,2例仍有胰腺炎发作,术前术后急性胰腺炎发作比较P=0.019,P<0.0 5.5例无结石患者术后全部无胰腺炎发作.结论 合并有结石的残余胆囊患者易发生急性胰腺炎,对患者行残余胆囊切除治疗可减少胰腺炎发作.     

Levels of the chemokines growth-related oncogene alpha and epithelial neutrophil-activating protein 78 are raised in patients with severe acute pancreatitis

BACKGROUND: Multiple organ dysfunction syndrome secondary to systemic leucocyte activation is the major cause of death following an attack of acute pancreatitis. Although plasma levels of interleukin (IL) 8 are known to be raised in acute pancreatitis, levels of other CXC chemokines such as growth-related oncogene (GRO) alpha and epithelial neutrophil-activating protein (ENA) 78, which are also potent neutrophil chemoattractants and activators, have not been measured.METHODS: Timed plasma samples were obtained from 51 patients with acute pancreatitis, 27 with a severe attack and 24 with mild disease according to the Atlanta classification. Samples were analysed to determine levels of C-reactive protein (CRP), IL-8, GRO-alpha and ENA-78.RESULTS: Plasma levels of IL-8, GRO-alpha and ENA-78 were increased in patients with severe as opposed to mild acute pancreatitis as early as 24 h following disease onset. Using cut-off levels of 7 pg/ml for IL-8, 70 pg/ml for GRO-alpha and 930 pg/ml for ENA-78, peak levels within the first 24 h of admission had an accuracy of 81, 71 and 87 per cent respectively in predicting the severity of an attack of acute pancreatitis.CONCLUSION: In patients with severe acute pancreatitis plasma levels of GRO-alpha and ENA-78 were raised in addition to those of IL-8, suggesting that all three chemokines are involved in the inflammatory response in this condition.     

Clinical evidence of pathogenesis in chronic pancreatitis

Chronic pancreatitis is a continuing inflammatory disease characterized by irreversible morphological change and, typically, by pain and permanent impairment of function. The pathogenesis of pancreatitis, either acute or chronic, is still controversial. There have been no widely accepted concepts to provide a reasonable explanation linking the known etiological factors and the pathophysiological aspects of the disease. Alcohol is undoubtedly the major etiological factor in most countries, and the relative importance of alcohol as a cause of chronic pancreatitis ranges from 40% to 90% in various countries. As fewer than 10% of alcoholics develop chronic pancreatitis, other nutritional or genetic influences are likely to be involved in the pathogenesis of alcoholic pancreatitis. Accessory pancreas incidentally found in patients with chronic alcoholic pancreatitis does not always have the pathological findings seen in the main pancreas. Integrity of the pancreatic duct seems to be another important factor for chronic alcoholic pancreatitis. Gene mutations of the cystic fibrosis transmembrane conductance regulator (CFTR), cationic trypsinogen, and pancreatic secretory trypsin inhibitor have been investigated in idiopathic chronic pancreatitis. Molecular and cell biology research during the past few years has elucidated pathophysiological factors that are involved in the pathogenesis of chronic pancreatitis, but cannot demonstrate a common pathway between etiological factors and the pathogenesis or development of the disease. Received: March 20, 2002 / Accepted: April 15, 2002 Offprint requests to: T. Hayakawa     

Changing pattern in aetiology of pancreatitis in an urban Swedish area.

Two groups of patients admitted with a first attack of acute pancreatitis are reviewed. The first group, consisting of 105 patients, was admitted between 1968 and 1969; the second group of 204 patients was admitted between 1974 and 1975. These groups were compared with one of 454 patients admitted between 1956 and 1960 whose details were published earlier by our unit (Edlund et al., 1968). The aim of this study was to determine whether the incidence of factors associated with pancreatitis within the population of the city of G?teborg had changed in the 20-year period. In the 1956--60 group gallstone disease was the main associated factor (68 per cent), but in the later groups alcohol-induced pancreatitis assumed the leading role (68 and 66 per cent respectively). Alcohol-induced pancreatitis tended to occur at a younger age than gallstone pancreatitis. Thirty-one per cent of 449 patients admitted with an acute attack of alcoholic pancreatitis in the two last periods of study had had previous attacks.     

Hyperlipidemia and pancreatitis

A total of 117 patients with pancreatitis were studied during the acute attack and after remission, and 32.5% were found to have hyperlipidemia, nearly all of type IV. There did not seem to be a relationship between hyperlipidemia and alcohol intake, although nearly 80% of the patients were alcoholics. No defect in triglyceride turnover could be demonstrated by intravenous fat tolerance tests or postheparin lipolytic activity measurements. No correlation was found between hyperlipidemia and steatosis of the liver or diabetes. It is suggested that the increase in serum triglyceride levels might be due to an increased synthesis or mobilization. It is also suggested that the hypertriglyceridemia does not directly induce an attack of pancreatitis, but might predispose a patient to develop pancreatitis when other provoking factors are also present.     

The theory of ''persisting'' common bile duct stones in severe gallstone pancreatitis.

There have been uncertainties as to the role of common bile duct (CBD) stones in severe gallstone pancreatitis. In order to resolve this, ERCP findings in 131 patients with acute pancreatitis were compared with predicted severity, clinical course and final outcome. Significant associations were found between 'persisting' CBD stones, coincidental acute cholangitis, predicted severity and actual outcome. There was evidence for acute obstruction of both the CBD and the pancreatic duct by CBD stones. The theory was therefore proposed that small migrating stones tend to initiate the attack, whereas larger 'persisting' stones tend to convert a mild attack into a severe attack. This hypothesis resolves previously irreconcilable theories and lends support to the use of urgent endoscopic sphincterotomy for treatment, but only in cases predicted to be severe.     

胆囊结石伴急性胆源性胰腺炎的微创治疗

目的 探讨胆囊结石伴急性胆源性胰腺炎（acute biliary pancreatitis,ABP）的微创治疗方法及手术时机。方法 回顾分析我院2008年5月～2013年5月胆囊结石伴ABP122例的临床资料。先保守治疗,磁共振胰胆管成像（MRCP）明确胆总管有无结石梗阻,104例未发现结石者急性胰腺炎恢复后行腹腔镜胆囊切除术（laparoscopic cholecystectomy,LC）。18例MRCP发现胆总管下段结石,行内镜逆行胆胰管造影（ERCP）＋十二指肠乳头括约肌切开（EST）取石＋鼻胆管引流（ENBD）治疗成功,再行LC。结果轻型106例,手术时间为发病后7～14天;重型16例,手术时间为发病后15～30天。无中转开腹、胆管损伤及死亡。其中107例随访5～8个月,无胰腺炎复发。结论对胆囊结石伴ABP应常规MRCP检查。未发现胆总管结石者待胰腺炎恢复后行LC;有胆总管结石伴梗阻者72小时内用十二指肠镜取出胆管下端嵌顿结石并ENBD,待胰腺炎恢复后再行LC;无梗阻者保守治疗胰腺炎恢复后,先行ERcP并取石,再行LC。手术时机应遵循“个体化”原则,一般轻型胰腺炎可在发病1～2周内手术。采用上述方法治疗胆囊结石伴ABP安全、有效、微创、可行。     

"Cocktail" therapy for acute pancreatitis: combined therapy of protease inhibitor, xanthine oxidase inhibitor and platelet activating factor antagonist in rat caerulein-induced pancreatis.

A supramaximal dose of caerulein (5 micrograms/kg.hr for 3.5 hours) caused an acute pancreatitis with marked hyperamylasemia and intense interstitial edema in rats. In this model of pancreatitis, the redistribution of lysosomal enzyme in acinar cells as well as the increased lysosomal and mitochondrial fragility were also observed. The combined therapy of a low molecular weight protease inhibitor, FOY, a synthetic platelet activating factor (PAF) antagonist, CV 6209, and a xanthine oxidase inhibitor, allopurinol produced more significant improvements in all the parameters examined than the therapy of any only one of these three agents, each only one therapy exerting a partial significant protective effect. These results indicate that several factors, such as unknown proteases activities, PAF and oxygen-derived free radicals may be involved in the pathogenesis of pancreatic injuries in this caerulein-induced pancreatitis. These results also suggest that such a combined therapy of different kinds of agents, whose therapeutic mechanisms are also different, is useful in the clinical treatment of acute pancreatitis.