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…     

急性胰腺炎的胰腺微循环紊乱及其治疗

从1889年Regiaal dFiu首先确定急性胰腺炎病至今．众多学者对该病病因进行了大量的临床和基础研究。国外近来的研究揭示；磷脂酶A和血栓素A2、胰蛋白酶和抗胰蛋白酶系统、溶酶体酶、氧自由基、细胞嗅稳定性和胰血循环障碍(包括胰腺微循环紊乱)等因素在急性胰腺炎发病中均起一定作用并相互联系。即使如此，对该病的确切发病机制目前尚未能予以阐明。鉴于近年来国外学者对胰腺微循环紊乱在急性胰腺炎发病中的作用倍加关注，本文就该问题以及针对胰腺微循环紊乱的治疗进行综述。     

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。     

早期改善胰腺微循环对重症急性胰腺炎的影响

目的　探讨早期改善胰腺微循环对治疗重症急性胰腺炎 (SAP)的疗效。方法　回顾性分析对比 1995～ 1998年 44例 (前期 )和 1998～ 2 0 0 1年 40例 (后期 )SAP患者的治疗效果。前期采取常规统一治疗 ,后期增加改善胰腺缺血及防止细胞钙超负荷的措施。结果　后期患者治愈率(85 .0 % )显著高于前期SAP患者治愈率 (68.2 % ) (P <0 .0 5 ) ;后期死亡率 (15 .0 % )、中转手术率(2 2 .5 % )、并发症率 (3 5 .0 % )明显地低于前期 (3 1.8%、40 .9%、5 4.5 % ) (P <0 .0 5 )。后期平均住院日 (2 2± 4)d ,较前期平均住院日 (3 2± 7)d明显缩短 (P <0 .0 5 )。结论　改善胰腺缺血和防止细胞钙超负荷有助于限制SAP恶化进程 ,改善SAP的预后     

急性胰腺炎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)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血中白细胞PECAM 1的表达。结果　与正常组相比 ,各实验组多形核白细胞 (PMN)PECAM 1的表达下调 ,在急性坏死性胰腺炎 (ANP)组差异有显著性 ,ANP 2h组 [(63 .0± 1 9.2 ) % ,P <0 .0 5] ,ANP 4、6h组[(38.1± 2 1 .2 ) %、(32 .9± 1 4 .5) % ,P <0 .0 0 1 ] ;淋巴细胞PECAM 1的表达轻度下调 ,差异无显著性(P >0 .0 5)。结论　胰腺微循环中PMNPECAM 1表达的下调说明PMN的激活 ,可促进PMN外渗 ;抑制PMNPECAM 1的过度表达可能是治疗AP和 /或阻断AP向坏死型转化的一种潜在途径     

中药WPY颗粒对急性胰腺炎小鼠胰腺微循环改变及血中TNF-α水平的影响

随着研究的深入，胰腺微循环改变，细胞因子、炎症介质在急性胰腺炎致病中的作用越来越受到人们的注意。因此阐明急性胰腺炎早期胰腺微循环改变和细胞因子的作用，对急性胰腺炎的防治有重要意义。     

微循环障碍与急性胰腺炎

急性胰腺炎(AP)尤其是重症急性胰腺炎(SAP)早期临床特点包括胰腺坏死、炎症因子激活、SIRS及MODS[1]。在AP早期发病过程中,胰腺组织缺血缺氧促进组织坏死的发生,触发AP后续系列病理改变。研究证实,胰腺局部灌注降低尤其是微循环障碍在AP病情进展过程中起重要作用[2]。针对微循环障碍的治疗有可能减少AP组织坏死的发生及降低病人病死率。本文就微循环系统在急性胰腺炎发病过程中所起作用做一介绍。1胰腺的微循环解剖胰腺具有丰富的血供,动脉系统包括直接发出于腹腔干及肠系膜上动脉的分支血管,动脉终末分支对胰腺血供具有调节作用。…     

川芎嗪对急性胰腺炎的作用

目的观察急性胰腺炎（AP）时大鼠体液因子和组织病理学的表达及川芎嗪对其的影响，探讨川芎嗪（TMP）对AP的治疗作用。方法采用十二指肠胆胰管逆行加压注射5％牛磺胆酸钠的方法制备大鼠AP模型，动态观察大鼠血浆丙二醛（MDA）、血栓素B2／6-酮-前列腺素F1a（TXB2／6-Keto—PGF1α）比值（TIP）、胰腺细胞凋亡指数（AI）、胰腺组织形态及大鼠72h死亡率、平均生存时间等各项指标。结果川芎组大鼠血浆MDA：1．45±0．22（12h）、T／P比值：6．52±0．96（12h）、胰腺组织病理评分：4．85±0．98（6h）、AI：9．88±0．98（6h）与胰腺炎组比较差距有统计学意义（P〈0．05）。结论TMP对AP治疗作用与其纠正TXA2、PGI2失衡，改善AP大鼠的微循环，减少自由基造成的损伤，诱导细胞凋亡，减少胰腺细胞坏死有关。     

急性坏死性胰腺炎胰腺血流改变意义的实验研究

目的探讨大鼠急性坏死性胰腺炎（ＡＮＰ）胰腺血流（ＰＢＦ）改变的意义。方法将４０只ＳＤ大鼠制成ＡＮＰ模型,２０只予生长抑素治疗,术前及术后６、１２小时以多普勒超声测定ＰＢＦ。取血测内毒素和ＴＮＦ一ａ,观察胰腺组织病理变化,分析ＰＢＦ与各指标的关系。另取６只正常鼠作对照。结果．ＡＮＰ大鼠ＰＢＦ减少,生长抑素治疗组ＰＢＦ明显改善,生存率提高。１２小时后ＰＢＦ速度与内毒素、ＴＮＦ－ａ和光镜病理评分密切相关。结论ＡＮＰ大鼠胰腺微区存在血运障碍,生长抑素有益于改善ＡＮＰ大鼠ＰＢＦ,多普勒超声检测ＰＢＦ能反映ＡＮＰ的严重程度。     

急性坏死性胰腺炎胰外器官微循环改变及乌司他丁的影响

目的 探讨急性坏死性胰腺炎(ANP)时肺、肾、肠微循环的变化及乌司他丁(UTI)的保护作用。方法 SD大鼠48只，随机均分为对照组、ANP组及UTI组。ANP组、UTI组于胰被膜下均匀注射5％牛磺胆酸钠制成ANP模型，对照组则注射等量生理盐水。UTI组于制模后即由股静脉缓慢注射UTI 10000u/kg，对照组及ANP组则注射等量生理盐水。分别于制模后2h及6h采用放射性生物微球法测定肺、肾及末端回肠组织的血流量变化。结果 与对照组相比，ANP组制模后2h及6h肺、肾、肠组织血流量显著减少(P＜0．05)；与ANP组相比，UTI组2h及6h各组织血流量均有明显增加(P＜0．05)。结论 微循环障碍是ANP胰外器官损害的重要原因之一，UTI对ANP时胰外器官微循环障碍有明显的保护作用。     

早期判断急性胰腺炎严重程度的方法探讨

目的:探讨早期判断急性胰腺炎严重程度的简便实用方法.方法:对1995～1996年收治的108例急性胰腺炎病例作回顾性分析.结果:体温≥38℃、血糖≥11.2mmol/L、血钙≤2mmol/L及胰外侵犯的出现可组成重症胰腺炎的预测体系,每一阳性指标计1分,≥2分者列为重症,其在本研究中的敏感性、特异性及准确性分别达95%、89.47%和91.53%.结论:该体系结合了急性胰腺炎的临床生化和形态学特点,较为简便、实用,入院早期即可作出判断.     

早期手术在暴发性急性胰腺炎治疗中的作用

目的探讨早期手术在暴发性急性胰腺炎（FAP）治疗中的作用。方法回顾性分析我院2003年9月至2004年12月收治的8例FAP患者的治疗情况。结果8例患者于人院及治疗过程中发生功能障碍的器官人均个数为3。非手术治疗1例死亡。手术治疗7例，1例死于腹腔室隔综合征合并肾功能衰竭，1例合并32周妊娠者术前胎儿死亡，其母亲存活；另5例术后并发腹腔脓肿经再手术治愈。结论早期手术能防治FAP患者MODS的继续发展，为其后续治疗创造机会，提高生存率。     

Platelet Function in Acute Experimental Pancreatitis

Acute pancreatitis (AP) is characterized by disturbances of pancreatic microcirculation. It remains unclear whether platelets contribute to these perfusion disturbances. The aim of our study was to investigate platelet activation and function in experimental AP. Acute pancreatitis was induced in rats: (1) control (n = 18; Ringer’s solution), (2) mild AP (n = 18; cerulein), and (3) severe AP (n = 18; glycodeoxycholic acid (GDOC) + cerulein). After 12 h, intravital microscopy was performed. Rhodamine-stained platelets were used to investigate velocity and endothelial adhesion in capillaries and venules. In addition, erythrocyte velocity and leukocyte adhesion were evaluated. Serum amylase, thromboxane A2, and histology were evaluated after 24 h in additional animals of each group. Results showed that 24 h after cerulein application, histology exhibited a mild AP, whereas GDOC induced severe necrotizing AP. Intravital microscopy showed significantly more platelet–endothelium interaction, reduced erythrocyte velocity, and increased leukocyte adherence in animals with AP compared to control animals. Thromboxane levels were significantly elevated in all AP animals and correlated with the extent of platelet activation and severity of AP. In conclusion, platelet activation plays an important role in acute, especially necrotizing, pancreatitis. Mainly temporary platelet–endothelium interaction is observed during mild AP, whereas severe AP is characterized by firm adhesion with consecutive coagulatory activation and perfusion failure. Parts of the results of this study were presented at the congress of the German Surgical Society, Berlin (May 2004), the Digestive Disease Week (May 2004), and the Annual Meeting of the American Pancreatic Association, Chicago (November 2004).     

微循环障碍在急性出血坏死性胰腺炎病程中的作用及丹参的治疗效果

用3%牛磺胆酸钠经胆胰管逆行注射,制成大鼠急性出血坏死性胰腺炎(AHNP)模型,并用丹参进行实验性治疗。结果:模型制作后6小时,对照组胰腺即出现严重的出血坏死及微血管破坏,血清胰酶活性显著升高(P<0.01),12小时后血清胰酶活性呈进行性降低,胰腺微血管及组织学病变则进行性加重;而丹参治疗组24小时时胰腺微血管损害及组织学病变显著改善(P<0.01)。作者认为微循环障碍是加重AHNP后期胰腺病变的重要因素,丹参能改善胰腺的微循环,对AHNP有一定治疗作用。     

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     

Treatment of Acute Pancreatic Pseudocysts After Severe Acute Pancreatitis

Treatment of acute pancreatic pseudocysts (APP) after an episode of severe acute pancreatitis (SAP) remains controversial. Both population heterogeneity and limited numbers of patients in most series prevent a proper analysis of therapeutic results. The study design is a case series of a large, tertiary referral hospital in the surgical treatment of patients with APP after SAP. An institutional treatment algorithm was used to triage patients with complicated APP and organ failure based on Sequential Organ Failure Assessment scores to temporizing percutaneous or endoscopic drainage to control sepsis and improve their clinical condition before definitive surgical management. Over a 10-year period of study (December 1995 to 2005), 73 patients with APP after an episode of SAP were treated, 43 patients (59%) developed complications (infection 74.4%, perforation 21%, and bleeding 4.6%) and qualified for our treatment algorithm. Percutaneous/endoscopic drainage was successful in controlling sepsis in 11 of 13 patients (85%) with severe organ failure and allowed all patients to undergo definitive surgical management. The morbidity (7 vs 44.1%, P = 0.005) and mortality rates (0 vs 19%, P = 0.04) were significantly higher in complicated vs uncomplicated APP. Acute pancreatic pseudocysts after SAP are unpredictable and have a high incidence of complications. Once complications develop, there is a significantly higher morbidity and mortality rate. In complicated APP with severe organ failure, percutaneous/endoscopic drainage is useful in controlling sepsis and allowing definitive surgical management.     

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。     

In Vivo Imaging of Human Pancreatic Microcirculation and Pancreatic Tissue Injury in Clinical Pancreas Transplantation

Pancreatitis remains to be a major complication following clinical pancreas transplantation. We performed orthogonal polarized spectral (OPS) imaging for direct in vivo visualization and quantification of human pancreatic microcirculation in six healthy donors for living donor liver transplantation and 13 patients undergoing simultaneous pancreas-kidney transplantation. We further determined the impact of microvascular dysfunction during early reperfusion on pancreatic graft injury. Exocrine and endocrine pancreatic impairment was determined by analysis of serum lipase, amylase and C-peptide levels. Compared to normal pancreas in liver donors (homogeneous acinar perfusion) functional capillary density (FCD) and capillary red blood flow velocity of reperfused grafts were significantly decreased. Elevated CRP concentrations on day 2 post-transplant and serum lipase and amylase levels determined on days 4-5 significantly correlated with microvascular dysfunction during the first 30 min of graft reperfusion. Post-transplant serum C-peptide also correlated significantly with pancreatic capillary perfusion. OPS imaging allows to intra-operatively assess physiologic pancreatic microcirculation and to determine microcirculatory impairment during early graft reperfusion. This impairment correlated with the manifestation of post-transplant dysfunction of both exocrine and endocrine pancreatic tissue. OPS imaging may be used clinically to determine the efficacy of interventions, aiming at attenuating microcirculatory impairment during the acute post-transplant reperfusion phase.