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。…     

急性水肿性胰腺炎内源性RAS的活化与局部微循环障碍关系的研究

目的探讨急性胰腺炎(AP)胰腺内源性肾素一血管紧张素系统(RAs)的活化与胰腺局部做循环障碍之间的关系，为进一步阐明AP时胰腺局部微循环损伤的机制提供实验依据：方法采用异硫氢酸荧光素(FTTC标记红细胞进行胰腺局部微循环活体观察，放免法检测局部微循环血浆及咦腺局部组织AngⅡ的含量变化。结果(1)与正常对照组相比，AEP组胰腺微循环血浆及局部组织AngⅡ的表达自2h开始上调，直至8h(P＜0．05)，其中自4h开始局部组织AngⅡ的含量明显高于血浆中AngⅡ的含量，差异有显著性(P＜0．05)；(2)与正常对照组相比，AEP组胰腺局部组织在疾病早期即开始出现血液流速减慢、流量减少等微循环障碍表现；(3)胰腺局部微循环血量随着RAS活化的上调而逐渐减少，相关分析显示两者呈显著线性相关(r=0．5449，P＜0．05)。结论胰腺局部组织的RAS参与AP早期的微循环损伤的病理过程，抑制或拮抗胰腺局部组织的RAS的活化可能有助于胰腺局部微循环障碍的改善。     

重症急性胰腺炎微循环障碍的治疗现状

胰腺微循环障碍是导致急性胰腺炎发展的重要因素,其在重症急性胰腺炎发病中的作用越来越引起人们的重视,针对改善胰腺微循环的治疗方法会减少胰腺组织的坏死程度和病变的演进。本文针对重症急性胰腺炎微循环障碍提出相关的治疗策略。     

酒精性胰腺炎致病机理的实验研究

探讨酒精性胰腺炎致病机理和钙通道阻滞剂对急性胰腺炎的治疗作用。方法　 5 0 %酒精对Wistar大鼠进行药物干预实验 ,并设立生理盐水对照组和Verapamil治疗组。检测胰腺、胃、肾脏局部微循环的血红蛋白含量和血氧饱和度变化 ,以及它们的病理学改变。结果　酒精使胰腺局部血氧饱和度显著下降 ,出现缺血性病理改变 ;对胃和肾脏无影响。Verapamil能对抗酒精对胰腺的损伤作用。 结论　酒精选择性损伤胰腺微循环结构和功能 ,导致胰腺发生缺血性病变 ;Verapamil能改善胰腺微循环障碍 ,对急性胰腺炎具有潜在的治疗作用。     

皮下注射蛙皮缩胆囊肽诱发急性胰腺炎的早期胰腺微循环损 …

探索急性胰腺炎实验动物模型的早期胰局部微循环损特征及其规律。方法用异硫硫氰酸荧光素标记红细胞活性微循环技术，微血管树脂和墨汁灌注光镜和扫描电镜技术，对蛙皮缩胆囊肽诱发ＡＰ早期胰腺局微循环改变进行动态观察。     

黄腐酸钠对大鼠重症胰腺炎胰腺微循环障碍的防治研究

目的 明确黄腐酸钠是否对大鼠重症胰腺炎胰腺微循环紊乱有防治效果。方法 采用胰腺被膜下注射5％牛磺胆酸钠液制备大鼠重症胰腺炎模型。结果 除正常组外．各组胰腺组织光镜病变程度随观察时间延长呈加重趋势．模型组胰腺病变程度明显重于同期黄腐酸钠治疗组(P<0．05)。空肠微循环改变结果近似上述胰腺微循环变化。黄腐酸钠治疗组同期血浆内皮素水平显著低于模型组(P<0．05)。上述结果提示各组胰腺微血流改变与其胰组织病理改变、血浆内皮素水平变化有相关性。结论 ①黄腐酸钠可明显改善重症胰腺炎微循环，并有控制病情发展的作用。②血浆内皮素变化是作为观察重症胰腺炎病变预后的客观指标之一。     

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。     

急性胰腺炎微循环障碍与治疗

急性胰腺炎(Acute pancreatits．AP)的病理生理一直被认为是由于胰酶激活以后所致胰腺及其周围组织的损伤。在治疗上则有针对性地用蛋白酶抑制剂，抑制胰腺分泌。但是大量实验和临床研究并未发现其有想象的效果。近年来人们开始注意到微循环障碍在AP中的作用。在轻症胰腺炎向重症急性胰腺炎(Severe acute pancreatitis,SAP)演进过程中，微循环障碍具有十分重要的作用。改善微循环，将可能提高AP的治疗效果。     

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。     

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     

Pancreatic ischaemia in experimental acute pancreatitis: mechanism, significance and therapy

Much clinical and experimental evidence suggests that pancreatic ischaemia in the early phase of acute pancreatitis is important in the development of pancreatic necrosis. While depletion of intravascular volume has often been assumed to be the main circulatory defect, an additional disturbance of pancreatic microcirculation has been demonstrated experimentally. Possible contributory mechanisms include chemical-induced vasoconstriction, direct injury of vessel wall, intravascular coagulation and increased endothelial permeability resulting in pancreatic oedema, haemoconcentration and impaired venous drainage. Pancreatic ischaemia as a consequence of these local effects seems to be responsible for the transition of mild pancreatitis to parenchymal necrosis. In experimental models the beneficial effect of various drugs and of sympathetic blockade has been ascribed to an improvement in pancreatic perfusion. Although effective volume therapy is generally accepted as the mainstay of conservative treatment in acute pancreatitis, the efficacy of different fluid preparations is still controversial, and simple fluid resuscitation has not been shown to prevent the development of parenchymal necrosis. The specific impairment of pancreatic microcirculation cannot be prevented merely by replenishment of intravascular volume with crystalloids, albumin or plasma despite normalization of macrohaemodynamics. In contrast, partial replacement of blood by dextran preparations has been shown to increase pancreatic perfusion by improving blood fluidity. Isovolaemic haemodilution in conjunction with conventional fluid therapy may provide a new and effective means of protecting the pancreas from secondary injury due to the early ischaemic phase of acute pancreatitis.     

Therapeutic effect of isovolemic hemodilution with dextran 60 on the impairment of pancreatic microcirculation in acute biliary pancreatitis.

Dextran of different molecular weight (Dx 40, Dx 60/70) has often been evaluated as adjunct treatment of experimental acute pancreatitis. A beneficial effect has been documented by a decrease in its lethality. However, the mechanism of action is poorly understood. A specific effect on the pancreatic microcirculation generally has not been documented and differentiation from unspecific improvement of pancreatic blood flow due to volume expansion has been difficult. This investigation was designed to quantify the effect of dextran on the impairment of pancreatic microcirculation during acute biliary pancreatitis by means of intravital microscopy. Dextran 60 (Dx 60, molecular weight 60,000) was chosen in light of the increase in vascular permeability in the early stage of pancreatitis as demonstrated previously in the same model. Isovolemic hemodilution, i.e., exchange of whole blood for Dx 60 was used as a mode of administration to achieve instantaneous onset of therapy without changes in intravascular volume. In the control group a progressive reduction of pancreatic capillary perfusion commenced 30 minutes after induction of acute pancreatitis, resulting in cessation of nutritive tissue perfusion after 3 hours. In the animals subjected to hemodilution, stabilization of the pancreatic microcirculation was accomplished throughout the observation period of 6 hours. Because volume-related effects could be excluded by the protocol and by monitoring central venous pressure and hematocrit, a specific effect of hemodilution with DX 60 on the pancreatic microcirculation is indicated by our results.     

Renal microcirculation in experimental acute pancreatitis of dogs--the effect of pancreatic protease inhibitor and dopamine

To understand the renal microcirculation in acute pancreatitis is important to know the pathophysiology of renal insufficiency frequently observed as one of multiple organ failures in severe acute pancreatitis. In mongrel dogs acute pancreatitis was experimentally introduced by autologous bile added trypsin injection into the pancreatic duct. The effect of new synthesized pancreatic protease inhibitor (PATM) and dopamine in a dose of 3mg/kg/hr and 10 micrograms/kg/min were investigated, respectively. In acute pancreatitis dogs, renal arterial blood flow and renal tissue blood flow immediately fell and gradually decreased in time course of experiment and renal vascular resistance increased from 2 hours after onset of pancreatitis. When pancreatic protease inhibitor (PATM) was infused in acute pancreatitis dogs, blood pressure and pulse pressure relatively preserved during the experiment. Renal blood flow and renal tissue blood flow were maintained during the first 1 hour and thereafter slightly decreased, however which was less than that of no PATM treated dogs. When dopamine was infused in acute pancreatitis dogs, blood pressure was maintained during the first 90 minutes thereafter remarkably decreased. Renal blood flow was maintained within 60 minutes, however it remarkably decreased at the end of the experiment. This study suggested that renal microcirculation was disturbed from early period of acute pancreatitis in dogs and pancreatic protease inhibitor (PATM) had a beneficial effect of maintain the renal microcirculation.     

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     

Systemic intravenous infusion of bovine hemoglobin significantly reduces microcirculatory dysfunction in experimentally induced pancreatitis in the rat

OBJECTIVE: To evaluate the effectiveness of bovine hemoglobin on pancreatic microcirculation and outcome in experimental acute rodent pancreatitis. SUMMARY BACKGROUND DATA: Stasis of the pancreatic microcirculation initiates and aggravates acute pancreatitis. Hydroxyethyl-starch (HES) has been shown to improve pancreatic microcirculation. Similarly, bovine hemoglobin might improve rheology due to its colloid effect, but additionally supplies oxygen to oxygen depleted pancreatic tissue. METHODS: In Wistar rats, severe acute pancreatitis was induced by administration of glucodeoxycholic acid i.d. and cerulein i.v. Pancreatic microcirculation was continuously monitored by fluorescence microscopy. Fifteen minutes after the initiation of acute pancreatitis, animals received either 0.8 mL bovine hemoglobin (Oxyglobin), HES, or 2.4 mL 0.9% NaCl i.v. at random. After 6 hours, animals were killed and histopathological damage of the pancreas was assessed using a validated histology score (0-16). RESULTS: In comparison to controls, pancreatic microcirculation improved significantly in the HBOC group (mean difference of capillary density 31.4%; standard error 5.6%; P < 0.001; 95% confidence interval for difference 17.5-45.3). HES was not as effective as HBOC substitution. The histology score revealed less tissue damage in the HBOC group [6.25 vs. 9.25 (3-8.5 vs. 8-10.75, P < 0.001)] in comparison to controls and also in comparison to the HES group [6.25 vs. 8 (3-8.5 vs. 6.5-10.25, P < 0.006)]. CONCLUSIONS: In severe acute pancreatitis, single i.v. injection of bovine hemoglobin improves pancreatic microcirculation and reduces tissue damage.     

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。     

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.     

遏制轻型急性胰腺炎向重症转化的非手术 治疗策略

目的 ：探讨遏制急性胰腺炎向重症转化的非手术治疗策略。方法 ：将4年间收治的286例轻型急性胰腺炎分为对照组和治疗观察组。对照组采取常规非手术治疗措施;观察组加用改善胰腺微循环，防治细胞钙超载和抑制胰酶的治疗方法。结果 ：对照组144轻型有20例转化为重症胰腺炎，14例发生全身性并发症;观察组142例轻型有8例转化为重症，2例出现全身性并发症。观察组重症患者血C-反应蛋白和Balthazar CT严重度指数在治疗后各时点较对照组明显降低。结论 ：在常规治疗的基础上加用改善胰腺微循环，防治细胞钙超载和抑制胰酶的治疗措施可能有助于阻止轻型急性胰腺炎向重症化发展。