Microcirculatory derangement and ischemia of the pancreas]

We present a review of the microvascular morphology of the pancreas and microstructure of the pancreatic lobule, and introduce our experimental results on pancreatic microcirculation following acute pancreatitis. Impairment of pancreatic microcirculation in the early phase of acute pancreatitis may play a key role in the progression of this disease. Possible contributory mechanisms include increased vascular permeability, reduced blood flow, leukocyte-endothelial cell interaction, and intravascular thrombus formation. We achieved direct-visualization and quantification of changes in microvascular permeability and leukocyte behavior in the pancreas with acute pancreatitis using an in vivo microscope system and off-line computer analysis. Bradykinin and oxygen radicals have been demonstrated to be involved in the increased vascular permeability in the early stage of cerulein pancreatitis. Gabexate mesilate (FOY) prevents the increase in vascular permeability, resulting in a decreased number of rolling leukocytes. Leukocyte adherence to the pancreatic microcirculation is a secondary event following permeability changes in acute pancreatitis. Leukocyte infiltration during aggravation of acute pancreatitis is mediated by leukocyte-endothelial cell interaction via leukocyte integrin CD11b/18. The diamino-pyridine derivative IS-741 inhibits the progression of pancreatic inflammation by down-regulating the expression of CD11b/18.     

Pancreatic microcirculation in acute pancreatitis

We present a review of the microvascular morphology of the pancreas and microstructure of the pancreatic lobule, and report our experimental results of the investigation of pancreatic microcirculation following acute pancreatitis. Impairment of pancreatic microcirculation in the early phase of acute pancreatitis may play a key role in the progression of this disease. Possible contributory mechanisms include increased vascular permeability, reduced blood flow, leukocyte-endothelial cell interaction and intravascular thrombus formation. Using an in-vivo microscope system and off-line computer analysis, we achieved direct visualization and quantification of changes in microvascular permeability and leukocyte behavior in pancreas with acute pancreatitis. Bradykinin and oxygen radicals have been demonstrated to be involved in the increase of vascular permeability in the early stage of caerulein pancreatitis. Leukocyte adherence to the vessels in the pancreatic microcirculation is a secondary event following permeability changes in acute pancreatitis. Leukocyte infiltration during exacerbation of acute pancreatitis is mediated by leukocyte-endothelial cell interaction via leukocyte integrin CD11b/18. Received for publication on Jan. 29, 1997; accepted on April 24, 1997     

Treatment with Met-RANTES reduces lung injury in caerulein-induced pancreatitis

BACKGROUND: Severe acute pancreatitis leads to a systemic inflammatory response characterized by widespread leucocyte activation and, as a consequence, distant lung injury. In CC chemokines the first two cysteine residues are adjacent to each other. The aim of this study was to evaluate the effect of Met-RANTES, a CC chemokine receptor antagonist, on pancreatic inflammation and lung injury in caerulein-induced acute pancreatitis in mice. METHODS: Acute pancreatitis was induced in mice by hourly intraperitoneal injection of caerulein. Met-RANTES was administered either 30 min before or 1 h after starting caerulein injections, and pancreatic inflammation and lung injury were assessed. There were five groups of eight mice each including controls. RESULTS: Treatment with Met-RANTES had little effect on caerulein-induced pancreatic damage. Met-RANTES, however, reduced lung injury when given either before administration of caerulein (mean(s.e.m.) lung myeloperoxidase (MPO) 1.47(0.19) versus 3.70(0.86)-fold increase over control, P = 0.024; mean(s.e.m.) microvascular permeability 1.15(0.05) versus 3.57(0.63) lavage to plasma fluorescein isothiocyanate-labelled albumin fluorescence ratio (L/P) per cent, P = 0.002) or after caerulein administration (lung MPO 1.96(0.27) versus 3.65(0.63)-fold increase over control, P = 0.029; microvascular permeability 0.94(0.04) versus 2.85(0.34) L/P per cent, P < 0.001). CONCLUSION: Treatment with Met-RANTES reduces lung damage associated with caerulein-induced pancreatitis in mice. Chemokine receptor antagonists may be of use for the treatment of the systemic complications of acute pancreatitis.     

急性胰腺炎大鼠TNF-α mRNA、IL-10 mRNA表达和胰腺细胞凋亡的研究

目的 探讨大鼠急性胰腺炎早期胰腺组织中TNF－αmRNA、IL－10mRNA的表达和细胞凋亡的变化规律。方法 以牛磺胆酸钠诱导20只大鼠急性水肿性胰腺炎（AEP）模型,20只急性坏死性胰腺炎（ANP）模型,另取10只正常大鼠作为对照。术后12h各处死10只大鼠,检测血清和胰腺组织中的TNF－α和IL－10水平,分析两者在胰腺组织中的mRNA较录水平,检测胰腺细胞的凋亡率。结果 正常、AEP和ANP组的细胞凋亡率分别为2．98％、17．29％和8．39％。制模后TNF－αm和IL－10增强ANP大鼠TNF－α表达增强。结论 急性胰腺炎大鼠胰腺组织中的TNF－α和IL－10的表达与其在血清和胰腺中的浓度成正比,胰腺本身可能就是产生细胞因子的主要器官。胰腺细胞凋亡率与疾病的严重程度呈负相关,凋亡是对胰腺损伤的良好反应。     

外源性溶血卵磷脂对急性胰腺炎大鼠血脑屏障通透性的影响

目的　探讨溶血卵磷脂(LPC)对胰腺炎(AP)大鼠血脑屏障(BBB)通透性的影响。方法　SD大鼠制成急性胰腺炎模型后随机分为: ( 1 )实验组,从大鼠的尾静脉注入LPC; ( 2 )对照I组,从尾静脉注入生理盐水; ( 3 )对照II组(假手术组),不制备AP模型,仅从尾静脉注入LPC。7 ~ 1 0d后应用辣根过氧化物酶-二氨基联苯氨显色法(HRP DAB法)检测3组大鼠BBB的通透性。结果　实验组HRP有局部血管外渗出,显示BBB通透性明显升高,对照I,II组BBB升高不明显,两者具有统计学差异(P< 0. 0 1, P< 0. 0 5 )。结论　LPC能增加胰腺炎大鼠BBB的通透性,可能与AP的胰性脑病发生有关。     

Early microcirculatory derangement in mild and severe pancreatitis models in mice

An in vivo microscopic technique was used to clarify the increase in microvascular permeability and enhanced leukocyte–endothelium interaction of pancreatic microcirculation in experimental pancreatitis of differing severity. Using bovine albumin fluorescein isothiocyanate (FITC) and carboxyfluorescein diacetate succinimidyl ester (CFDASE) as tracers, the change in permeability and the behavior of leukocytes in the acinar microcirculation were quantified during the initial 1, 2, 6, and 12 h after the induction of caerulein pancreatitis in mice. Cold stress was added to produce the severe model. It was revealed that the early microcirculatory changes in the pancreas of caerulein pancreatitis included the increased permeability of endothelial lining and an accumulation of extravasated fluid in the perilobular space, which were more severe if cold stress was added. A decrease in flow velocity was also noted 2 h after the onset of severe pancreatitis. Leukocyte adherence to the endothelial cells was not observed during the first 12 h in either model of severity. In contrast, observation of the hepatic microcirculation revealed a significant number of adherent leukocytes 2 h after the induction of severe pancreatitis. These results suggest that during the early course of acute pancreatitis, leukocyte adherence in the pancreatic microcirculation is a secondary event following the increase in pancreatic vascular permeability. Received: February 21, 2000 / Accepted: March 6, 2001     

Possible mechanisms of acute pancreatitis induced by ethanol

We investigated the effect of intravenous and intragastric ethanol on pancreatic duct pressure, duct permeability to dextran molecules (20,000 molecular weight), and on the development of acute pancreatitis in an experimental model of the disease. Intragastric ethanol caused a small increase in pancreatic duct pressure (6 to 7 mm Hg) and an increase in duct permeability to dextran. Intravenous ethanol with exclusion of the sphincter of Oddi did not increase pancreatic duct pressure or permeability. Intravenous ethanol and intragastric normal saline solution altered neither pressure nor permeability. Artificial elevation of pancreatic duct pressure alone with no ethanol had no effect on duct permeability. However, when intravenous ethanol was given to produce similar systemic concentrations as achieved in the intragastric experiments (250 mg/dl) and duct pressure was artificially raised, duct permeability was increased. Ethanol concentrations similar to those found in peripheral blood were detected in secretin-stimulated pancreatic juice. Perfusion of the pancreatic duct with activated pancreatic enzymes after intragastric but not intravenous ethanol (that is, only in animals with increased duct permeability) caused acute edematous pancreatitis. Our results confirmed that increased duct permeability was necessary to produce acute pancreatitis in this model, and that this increase in permeability resulted from both a small increase in duct pressure and probably from the toxic metabolic effects of ethanol.     

一种研究急性胰腺炎加重病理机理的动物模型

介绍一种急性水肿性胰腺炎（ＡＥＰ）向坏死性胰腺炎（ＡＮＰ）转变的大鼠模型。１０７只ＳＤ大鼠随机分为假手术组、ＡＥＰ组和ＡＮＰ组。ＡＥＰ通过胰管结扎、外分泌刺激诱发。在ＡＥＰ模型基础上静注大剂量Ｄｅｘｔｒａｎ１１０诱发ＡＮＰ。结果显示：血清淀粉酶水平在ＡＥＰ、ＡＮＰ组明显增高，胰腺泡细胞胞浆游离钙离子浓度在ＡＮＰ诱发后持续增高；胰腺出血、实质坏死、钙沉积在ＡＮＰ组常见。超微结构显示ＡＮＰ组胰毛细血管内皮剥脱、坏死。由此表明，胰腺缺血可能通过腺泡细胞钙超负荷的作用促发ＡＥＰ向ＡＮＰ转变。该大鼠模型因临床联系较好、病变渐进，不失为一种从细胞和分子水平研究急性胰腺炎加重病理机理的动物模型     

大鼠急性胰腺炎凋亡相关微小RNA表达谱分析

目的 分析大鼠急性胰腺炎凋亡相关微小RNA(miRNA)的表达谱.方法 将SD大鼠36只随机分为:空白对照组、急性水肿性胰腺炎组(AEP)和急性坏死性胰腺炎组(ANP).AEP组模型采用L-精氨酸150 mg/kg腹腔注射建立,ANP组模型采用L-精氨酸2400 mg/kg腹腔注射建立;各组于造模后12 h,检测血清淀粉酶、脂肪酶含量;TUNEL法检测胰腺组织腺泡细胞的凋亡,对胰腺组织进行病理学评分,各组选择2例应用miRNA芯片技术检测miRNA的表达,筛选表达差异miRNA,进行层次聚类分析.结果 与ANP组比较,AEP组的血清淀粉酶、脂肪酶和病理学评分明显降低(P＜0.05),胰腺腺泡细胞凋亡指数显著升高(P＜0.05);实验组与空白对照组比较各指标差异有统计学意义(P＜0.05).miRNA芯片分析:与空白对照组比较,ANP组和AEP组表达差异均在2倍以上;且与ANP组比较,AEP组表达差异在2倍以上,差异有统计学意义(P＜0.05)的miRNA认为是凋亡相关miRNA(AA miRNA).表达差异AA miRNA共计有8条,其中与ANP组比较,2倍以上升高AA miRNA的共5条;2倍以上降低AA miRNA的共3条.结论 急性胰腺炎发病过程某些miRNA可能参与胰腺炎腺泡细胞凋亡过程的凋节.

Abstract：

Objective To analyze micro RNA (miRNA) expression profile relating to rats apoptosis due to acute pancreatitis.Methods Thirty-six SD rats are randomly divided into:blank control group,acute edematous pancreatitis (AEP) and acute necrosis pancreatitis (ANP).AEP group model is established by L-arginine(150mg/kg) intraperitoneal injection and ANP group model is established by L-arginine (2400 mg/kg) intraperitoneal injection;inspect every group's serum amylase and lipase content 12 h after molding;inspect the apoptosis of acinar cell in pancreatic tissue by TUNEL method and give the pancreatic tissue the pathological score;choose 2 from every group to inspect miRNA expression by miRNA chip technology,and screen out the miRNA with differential expression and make hierarchical clustering analysis.Results Compared with ANP group,AEP group's serum amylase,lipase and pathological score decline dramatically (P＜0.05 ),and apoptosis index of pancreatic acinar cells increases significantly (P＜0.05 );there are dramatic differences between the experimental group indexes and blank control group indexes (P ＜0.05 ).miRNA chip analysis:In comparison with blank control group,the expression differences of ANP group and AEP group are both more than 2 times;in comparison with ANP group,the expression difference of AEP group is more than 2 times,and the miRNA with dramatic difference (P ＜0.05 ) by statistical analysis is regarded as apoptosis associated miRNA ( AA miRNA).There are 8 AA miRNAs with expression difference,and compared with ANP group,5 increase more than 2 times;3 reduce more than 2 times.Conclusion In the process of acute pancreatitis,pathophysiologic changes are associated with miRNA expression profile,and some miRNA may participate in the regulation of pancreatic acinar cell apoptosis process.     

Disturbances of the microcirculation in acute pancreatitis

BACKGROUND: Severe acute pancreatitis is characterized by pancreatic necrosis, resulting in local and systemic inflammation. Pancreatitis affects both the systemic and pancreatic vasculature. This review focuses on the underlying processes involved in the changes of microvascular anatomy following acute pancreatitis. METHODS: A Medline/PubMed search (January 1966 to December 2005) with manual cross-referencing was conducted. All relevant articles investigating the pancreatic microcirculatory anatomy and the effect of pancreatitis on the microcirculation were included. RESULTS: The pancreas is susceptible to ischaemic insult, which can exacerbate acute pancreatitis. There is also increasing evidence of pancreatic and systemic microvascular disturbances in the pathogenesis of pancreatitis, including vasoconstriction, shunting, inadequate perfusion, and increased blood viscosity and coagulation. These processes may be caused or exacerbated by ischaemia-reperfusion injury and the development of oxygen-derived free radicals. CONCLUSION: Acute pancreatitis impairs the pancreatic and systemic microcirculation, which is a key pathological process in the development of severe necrotizing disease.     

中药复方TCMP-1对急性胰腺炎血小板内皮细胞粘附分子-1表达变化的研究

目的 探讨急性水肿性胰腺炎(AEP)血小板内皮细胞粘附分子-1(PECAM-1)表达的变化规律及中药复方TCMP-1对AEP的治疗作用。方法 Wistar大鼠54只,诱发AEP动物模型,并给予TCMP-1干预,用流式细胞仪分析脾静脉血中多形核白细胞(PMN)PECAM-1的表达。结果 (1)在AEP自然病程组中,外周循环和胰腺微循环PMN PECAM-1的表达水平在AEP 2、4 h组相近,自AEP 4 h组开始,外周循环PECAM-1的表达上调直至AEP 8 h组;胰腺微循环PECAM-1的表达下调直至AEP 8 h组;在AEP 8 h组,PMN PECAM-1的表达有显著性差异(P<0.05)。(2)在AEP 8 h治疗组与AEP 8 h自然病程组中,体循环PMN PECAM-1的表达有显著性差异(P<0.05)。结论 (1)下调体循环PMN PECAM-1的表达水平或抑制PMN PECAM-1的过度表达,可以阻止胰腺微循环中PMN与内皮细胞的粘附。(2)抑制PMN PECAM-1的过度表达是中药复方TCMP-1实现其疗效作用的主要机制之一。     

Pancreatic duct pressure, duct permeability and acute pancreatitis

The relationship between pancreatic duct pressure, duct permeability to macromolecules and the development of acute pancreatitis was studied in a cat model. Perfusion of the pancreatic duct with 15 mM glycodeoxycholic acid, ethanol administration, or secretagogue-stimulated pancreatic secretion against greater than 50 per cent duct obstruction resulted in an increase in peak pancreatic duct pressure in all animals. Duct permeability to 20,000 molecular weight dextran molecules was increased in 22 of 29 experimental animals compared with two of 22 control animals (P less than 0.01). Perfusion of the pancreatic duct with activated pancreatic enzymes resulted in acute pancreatitis in 24 of 29 experimental animals compared with three of 22 control animals (P less than 0.01). These results suggest that pancreatic ductal hypertension, resulting in increased ductal permeability to large molecules, may be a common early event in gallstone and alcoholic pancreatitis.     

降钙素基因相关肽对急性胰腺炎胰腺微循环的影响

目的 研究降钙素基因相关肽（CGRP）对急性胰腺炎（AP）胰腺微循环及血管通透性的作用。方法 测定各组SD大鼠胰腺血流、微血管通透性，并对胰腺病理切片进行评分、对比。结果 （1）AP时胰腺血流发生显著改变；在AP模型建立前及过程中皮下注射CGRP，胰腺血流量、血液流速显著增加，胰腺病变程度减轻；在AP模型建立后注射CGRP，上述指标无改善。（2）AP时皮下注射CGRP，可使胰腺微循环血管通透性显著降低。结论 在AP模型建立前或同时皮下注射CGRP可以增加胰腺的血流量、血液流速，降低微血管通透性，减轻胰腺组织的损伤程度。     

Is procalcitonin a reliable marker for the diagnosis of infected pancreatic necrosis?

BACKGROUND: Infected necrosis in acute pancreatitis is the main factor in determining the prognosis of the disease. Early and accurate diagnosis of infected pancreatic necrosis might decrease mortality. The aim of the present study is to identify a reliable marker for the onset infection in three different experimentally induced pancreatitis models. METHODS: Ninety female Wistar albino rats were randomly divided into nine groups. In three different experimental models, including cerulein induced acute oedematous pancreatitis (AEP), sterile pancreatic necrosis due to taurocholate-induced acute pancreatitis (SPN) and infected pancreatic necrosis taurocholate-induced acute pancreatitis (IPN). Serum levels of procalcitonin (PCT), C-reactive protein (CRP), tumour necrosis factor a (TNF-alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8), amylase were measured. The degree of pancreatic damage also evaluated pathologically. RESULTS: Procalcitonin levels were increased significantly in AEP, SPN and IPN compared to control groups (P < 0.05). PCT and IL-6 level were the highest in the IPN group (P < 0.05). Serum amylase, CRP, TNF-alpha, IL-2, and IL-8 levels were similar between IPN and SPN groups (P > 0.05), but higher than in other groups. The results of histological evaluation also correlated with the advent of the disease. CONCLUSION: Procalcitonin and IL-6 acts as reliable acute phase reactant in an experimental model of AEP, SPN and IPN in the rat. PCT and IL-6 combination might be surrogate marker of infected pancreatic necrosis and should be preferred to other markers assay especially in severe pancreatitis.     

Thromboxane A2 receptor antagonist prevents pancreatic microvascular leakage in rats with caerulein-induced acute pancreatitis

This study was designed to evaluate the protective effect of thromboxane A2 (TXA2) receptor antagonist, seratrodast, against pancreatic injuries during acute pancreatitis. Acute pancreatitis was induced in rats by intravenous infusion of a supramaximal dose of caerulein (5 microg/kg x h for 4 h). In this model, marked hyperamylasemia, a significant increase in pancreatic water content, and a significant increase in pancreatic micro-vascular leakage of Evans blue dye were observed. Pancreatic subcellular redistribution of a lysosomal enzyme, cathepsin B from the lysosomal fraction to the zymogen fraction as well as a significant increase in pancreatic trypsin content were also observed. Pretreatment with seratrodast at a dose of 2 mg/kg (twice, 8 and 4 h before caerulein infusion) significantly inhibited these pancreatic injuries including hyperamylasemia, increased pancreatic microvascular leakage, redistribution of cathepsin B and increased pancreatic trypsin content. These results suggest that TXA2 may be involved in the pathogenesis of acute pancreatitis in the early stage of the disease and that TXA2 receptor antagonist might be of therapeutic value for treatment of acute pancreatitis.     

急性胰腺炎外周循环和胰腺微循环血小板内皮细胞粘附分子-1的表达

目的　探讨急性胰腺炎 (AP)外周循环和胰腺微循环中血小板内皮细胞粘附分子 1(PECAM 1)表达的变化规律。方法　Wistar大鼠 48只 ,诱发AP动物模型 ,用流式细胞仪分析脾静脉和下腔静脉血中多形核白细胞 (PMN )PECAM 1的表达。结果　 ( 1)在急性水肿性胰腺炎(AEP)动物模型中 ,外周循环和胰腺微循环PMNPECAM 1的表达水平在AEP 2、4h组相近 ,自 4h开始 ,外周循环PMNPECAM 1的表达上调直至 8h ;胰腺微循环PMNPECAM 1的表达下调直至 8h ,在AEP 8h组 ,差异有显著性 ( P <0 .0 5 )。 ( 2 )在急性坏死性胰腺炎 (ANP)模型中 ,胰腺微循环PMNPECAM 1的表达下调 ;外周循环组PMNPECAM 1的表达未见明显变化 ,在ANP 4、6h组 ,差异有显著性 (P <0 .0 5 )。结论　AEP胰腺微循环和外周循环PMNPECAM 1的表达呈逆向性 ,在胰腺微循环呈下调趋势 ,在外周循环呈上调趋势 ;ANP胰腺微循环PMNPECAM 1的表达呈加速性下调 ,该结果显示 ,在ANP早期 ,抑制PMNPECAM 1的过度表达可能有助于改善AP病理改变。     

Anti-tumor necrosis factor antibody augments edema formation in caerulein-induced acute pancreatitis

The pathogenesis of acute pancreatitis is incompletely defined, but the outcome is determined in part by an acute inflammatory process. Pancreatitis-associated inflammation appears to play a role in the local retroperitoneal injury as well as in the associated dysfunction of remote organs such as the lung. Tumor necrosis factor (TNF) appears to be a proximal mediator of the inflammatory response. In this study, anti-TNF antibody was administered to rats with caerulein-induced pancreatitis to determine if the observed increases in pancreatic and pulmonary microvascular permeability were related to plasma TNF activity. In contrast to the expected findings, blockade of TNF activity was found to increase the amount of edema formation in both the pulmonary and pancreatic microvascular beds. The mechanism is not known; however, blockade of TNF-induced down regulation of phagocytic cell activity, ablation of TNF-dependent feedback inhibition of other cytokines, failure of induction of endogenous antioxidant systems, or inactivation of the TNF control of microvascular tone are all possible explanations. This is potentially an important observation as clinical strategies are now being developed to modify the inflammatory response in ways presumed advantageous to an injured host.     

Glutamine stabilizes intestinal permeability and reduces pancreatic infection in acute experimental pancreatitis

Intestinal barrier failure and subsequent translocation of bacteria from the gut play a decisive role in the development of systemic infections in severe acute pancreatitis. Glutamine (GLN) has been shown to stabilize gut barrier function and to reduce bacterial translocation in various experimental settings. The aim of this study was to evaluate whether GLN reduces gut permeability and bacterial infection in a model of acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced in 50 rats under sterile conditions by intraductal infusion of glycodeoxycholic acid and intravenous infusion of cerulein. Six hours after the induction of pancreatitis, animals were randomly assigned to one of two groups: standard total parental nutrition (TPN) or TPN combined with GLN (0.5 g/kg⁻¹/day⁻¹). After 96 hours, the animals were killed. The pancreas was prepared for bacteriologic examination, and the ascending colon was mounted in a Ussing chamber for determination of transmucosal resistance and mannitol flux as indicators of intestinal permeability. Transmucosal resistance was 31% higher in the animals treated with GLN-supplemented TPN compared to the animals given standard TPN. Mannitol flux through the epithelium was decreased by 40%. The prevalence of pancreatic infections was 33% in animals given GLN-enriched TPN as compared to 86% in animals receiving standard TPN (P < 0.05). Adding GLN to standard TPN not only reduces the permeability of the colon but decreases pancreatic infections in acute necrotizing pancreatitis in the rat. This confirms previous reports that GLN decreases bacterial translocation by stabilizing the intestinal mucosal barrier. The present findings provide the first evidence suggesting that stabilizing the intestinal barrier can reduce the prevalence of pancreatic infection in acute pancreatitis and that GLN may be useful in preventing septic complications in clinical pancreatitis.     

内源性一氧化氮对急性胰腺炎大鼠胰腺微血管通透性的影响

目的 探讨内源性一氧化氮（NO）对急性坏死性胰腺炎大鼠胰腺炎大鼠胰腺微血管通透性的影响。方法 以5%牛磺胆酸钠溶液胰胆管注射（1ml/kg）制成大鼠急性坏死性胰腺炎模型,以工具药L-硝基精氧酸（L-NNA）和内源性NO的阻断Evans Blue的漏出代表微血管的通透性,观察内源性NO对胰腺组织损伤程度、胰腺内Evans Blue漏出等的影响。结果 牛磺胆酸钠胆管注射造成大鼠胰腺组织明显坏死和炎性细胞浸润,以及血清淀粉酶浓度升高、胰腺湿/干重比率产加和明显的胰腺组织内Evans Blue积聚。以L-NNA（12.5mg/kg）阻断内源性NO后,胰腺组织坏死和炎性细胞浸润进一步加重,并使血清淀粉酶浓度升高,胰腺湿/干重比率增加,Evans Blue的漏出率也较之单纯胰腺炎组大鼠明显增加。结论 内源性NO具有胰腺保护作用,其保护机制可能与维持胰腺微血管的完整性有关。     

胰腺炎微循环障碍加重过程中血管内皮生长因子的表达及意义

目的:探讨在胰腺炎微循环障碍加重的过程中,血管内皮生长因子(VEGF)的表达情况及其意义。方法:选取实验用大鼠共30只,其中15只大鼠处理为急性水肿型胰腺炎(AEP),另外15只大鼠则处理为胰腺炎微循环障碍加重后的急性坏死型胰腺炎(ANP),测量2组大鼠血清中VEGF的含量,检测VEGF在胰腺组织中的表达情况,同时将胰腺置于光学显微镜下,观察病理改变。结果:2组血清中均有较高的VEGF含量,ANP组高于AEP组(P<0.05);ANP组大鼠胰腺组织中的VEGF表达明显升高,与AEP组相比差异有统计学意义(P<0.01);光学显微镜下观察2组大鼠的胰腺组织,AEP组间质充血,存在坏死的腺泡灶,而ANP组则出现间质的出血,腺泡灶也存在大范围的坏死,同时大量红细胞沉积,坏死更加明显。结论:在胰腺炎微循环障碍加重之后,VEGF出现明显的高表达,在临床上可以作为疾病加重的指标之一。