特异性血栓素合成酶抑制剂对急性坏死性胰腺炎犬胰腺及肺损伤的影响

目的观察特异性血栓素合成酶抑制剂对急性坏死性胰腺炎（ANP）犬胰腺及肺损伤的影响,探讨其作用机制。方法20只健康雄性杂种犬按数字表法随机分为对照组（4只）、ANP组（8只）及特异性血栓素合成酶抑制剂（商品名：丹奥）治疗组（治疗组,8只）。采用胰管内逆行注射5％牛黄胆酸钠及胰蛋白酶混合液的方法制备ANP模型,治疗组于制模成功后2h起静脉输注2mg／kg体质量的丹奥,每天2次,连用7d。术后动态监测各组血清钙、超敏C反应蛋白（HCRP）、血栓素A2（TXA2）、前列环素（PGI2）水平。7d后处死动物,取胰腺及肺组织行病理学检查,并评分。结果对照组胰腺及肺组织无明显病理改变;ANP组胰腺及肺损伤严重;治疗组胰腺及肺组织损伤较ANP组减轻。对照组、ANP组、治疗组的胰腺病理评分分别为（1．25±0．96）、（7．00±2．39）、（4．63±1．19）分;肺组织病理评分分别为（0．75±0．50）、（7．13±1．55）、（4．88±0．83）分,ANP组、治疗组的胰腺、肺组织病理评分均显著高于对照组,而治疗组的评分又较ANP组显著降低（P值均〈0．05）。对照组术后1d的血清钙、HCRP、TXB2、keto—PGFla水平及TXB2／keto—PGFla比值分别为（2．45±0．07）mmol／L、（30．36±4．29）mg／L、（345．8±46．8）pg／ml、（187．8±18．6）pg／ml、1．85±0．16;ANP组为（2．21±0．08）mmol／L、（72．04±10．22）mg／L、（1227．3±118．2）pg／ml、（368．8±64．4）pg／ml、3．33±0．19;治疗组为（2．32±0．08）mmol／L、（66．51±4,28）mg／L、（1179．5±116．3）pg／ml、（371．8±65．2）pg／ml、3．17±0．18。ANP组与治疗组术后血清钙水平较对照组显著下降,而其他指标显著升高,差异均具有统计学意义（P值均〈0．01）。治疗组血清钙水平显著高于ANP组,血HCRP水平显著低于ANP组,差异有统计学意义（P〈0．05或〈0．01）。结论应用特异性血栓素合成酶抑制剂治疗后ANP犬的胰腺及肺脏损伤程度减轻,其机制与阻断TXA2合成,纠正TXA2／PGI2的比例失衡,改善胰腺及肺组织微循环有关。     

实验性大鼠急性坏死性胰腺炎合并肺损害TXA2，PGI2的变化

急性坏死性胰腺炎部分肺损害，如何防治这种致死性并发症，仍是胰腺外科领域中的一项重要课题，关键在于其病理机制尚未完全阐明．近年来，前列环素Ｉ２（Ｐｒｏｓｔａｇｌａｎｄｉｎ，Ｉ２，ＰＧＩ２）和血栓素Ａ２（ＴｈｒｏｍｂｏｘａｎｅＡ２，ＴＸＡ２）在感染、免疫...     

外源性IL-10对急性坏死性胰腺炎大鼠胰腺及肝组织STAT3表达的影响

目的:探讨外源性人重组白介素10(IL-10)在急性坏死性胰腺炎(ANP)大鼠胰腺及肝组织中对信号转导和转录激活因子3(STAT3)表达的影响.方法:92只健康SD♂大鼠随机分为正常对照组(C组,n=24)、ANP组(A组,n=36)和IL-10后干预组(Ⅰ组,n=32).采用腹腔注射左旋精氨酸(L-arginine)...     

早期肠内营养对急性坏死性胰腺炎犬胰腺外分泌功能的影响

目的 观察早期肠内营养(EN)对ANP犬胰腺外分泌功能的影响.方法 采用胰管内注人5%牛磺胆酸钠胰蛋白酶混合液1 ml/kg体重诱导ANP犬模型.完全随机法分为胃肠外营养组(TPN)、十二指肠高能营养多聚合剂组(DP)、十二指肠营养混悬液组(DN)、空肠高能营养多聚合剂组(JP)和空肠营养混悬液组(JN),每组5只.诱导ANP后24 h开始实施各种营养支持,维持5 d.造模后每天抽血测淀粉酶、LDH、脂肪酶及SEC、CCK、胃泌素含量.每日于EN或TPN开始后收集3 h胰液,测定其分泌量、蛋白酶、淀粉酶、脂肪酶、HCO31、K+、Na-、Cl-含量.实验第7天处死动物,取胰腺组织行病理学和超微结构检查.结果 各组血清淀粉酶、LDH、脂肪酶、CCK活性、胰液分泌量及K+、Na+、Cl1量均无显著差异.十二指肠营养组血浆胃泌素、SEC,胰液中HCO3-、淀粉酶、脂肪酶、蛋白酶含量均显著高于TPN组(P<0.05).空肠营养组的上述指标均显著低于十二指肠营养组(P<0.05),与TPN组无显著差异.JP组的血浆胃泌素含量及胰液的HCO3-、淀粉酶、脂肪酶和蛋白酶含量均显著低于JN组(P<0.05).高能营养多聚合剂组的上述指标低于营养混悬液组(P<0.05).各组问胰液分泌量及K+、Na+、Cl-量均差异无显著意义(P>0.05).各组胰腺病理改变相似.空肠营养组胰腺腺泡细胞胞质内酶原颗粒数量与密度未明显低于TPN组.结论 近端空肠内低脂要素营养对胰腺外分泌无增强效应,是安全可行的.     

巯基物质对急性坏死性胰腺炎胰腺细胞保护作用的实验研究

细胞保护的概念于 2 0世纪 70年代由Ｒｏｂｅｒｔ[1 ] 提出后引起广泛关注。针对胃黏膜细胞保护机制进行了大量的基础和临床研究 ,但有关胰腺细胞保护方面的研究相对较少。本研究旨在探讨在急性坏死性胰腺炎 (ＡＮＰ)时巯基物质对胰腺细胞的保护作用及其抗氧化机制。一、材料和方法1 主要试剂药物和仪器 :注射用硫普罗宁、牛磺胆酸钠等均购自北京化学试剂公司 ,分光光度仪、ＤＰＵ 6荧光分光光度仪等均由北京市神经外科研究所提供。2 实验方法 :雄性Ｗｉｓｔａｒ大鼠 1 0 5只 ,随机分为 3组 ,Ａ组 :ＡＮＰ +ＮＳ组 (45只 ) ;Ｂ组 :ＡＮＰ …     

急性胰腺炎与白介素10

急性胰腺炎 (ａｃｕｔｅｐａｎｃｒｅａｔｉｔｉｓ ,ＡＰ)是外科中较为常见的疾病 ,其病因在我国以胆源性多见。在早期由于对该病的认识不足 ,多采取早期而彻底的手术。随着国内外学者对该病的发病机理的不断认识和完善 ,以及大量的临床实践 ,对该病的治疗渐趋保守 ,避免了过早过大的手术。尤其是近年来对细胞因子的研究 ,更是为急性胰腺炎的治疗提供了一种潜在而有效的治疗手段 ,以期能提高疗效 ,缩短疗程 ,降低死亡率。一、急性胰腺炎的发病机理 :急性胰腺炎的发病机理至今尚未完全阐明 ,已为大家所接受的有以下几点 :1 消化酶的自身消化…     

巨噬细胞移动抑制因子在急性坏死性胰腺炎发病中的作用

目的 探讨巨噬细胞移动抑制因子(MIF)在实验性急性坏死性胰腺炎(ANP)发病机制中的作用以及抗炎细胞因子白介素-10(IL-10)对其的影响和意义.方法 92只大鼠随机分为对照组、ANP组和IL-10治疗组.腹腔注射左旋-精氨酸制作ANP模型.治疗组于末次精氨酸注射后第2、5、8 h腹腔内注射IL-10 10 000U.各组再分4 h、12 h、24 h和36 h点.检测血清巨噬细胞移动抑制因子(MIF)水平以及胰腺和肺组织的MIF表达.结果 ANP组MIF在造模后4 h已升至高值,并持续维持在较高水平,波动于(117.82 ± 15.73)μg/L至(120.97 ± 11.24)μg/L,显著高于对照组的血清MIF浓度(P ＜0.01或P ＜0.05);治疗组各时点血清MIF浓度低于ANP组(P ＜0.05).对照组大鼠胰腺组织的外分泌部、肺组织的支气管上皮细胞及肺泡细胞有MIF弱表达,ANP组和治疗组胰腺及肺组织MIF阳性细胞数增加、染色明显增强.结论 (1)MIF水平在ANP早期明显升高,ANP时肺及胰腺组织中MIF表达增强,提示MIF参与了大鼠ANP及肺损伤的发病;(2)抗炎细胞因子IL-10对血清及胰腺和肺组织的MIF水平有抑制作用,IL-10可能减轻实验性ANP的胰腺及肺的损害,对胰腺及肺组织有一定保护作用.     

外源性IGF—I对急性坏死性胰腺炎大鼠胰腺病理损伤的影响

重症急性胰腺炎（severe acute panereatitis,SAP）的发病机制是一个复杂的、多因素参与的病理生理过程。参与SAP发生发展过程中的炎症性细胞因子包括TNF—α、IL-1β、IL-6、IL-8、血小板活化因子等,抗炎症细胞因子包括TGF-β和IL—10等。本实验应用外源性生长调节素（insulin—like growth factorI,IGF—I）干预治疗急性坏死性胰腺炎（ANP）大鼠,以观察其对ANP大鼠血浆TNF-α、IL-10水平及胰腺病理损伤的影响。     

酪蛋白空肠灌注对急性坏死性胰腺炎大鼠胰腺外分泌的影响

目的 观察空肠内灌注酪蛋白对急性坏死性胰腺炎(ANP)大鼠胰腺外分泌的影响,并初步探讨其神经机制.方法 30只SD大鼠按随机数字法分为对照组、ANP组和肠内营养组.后2组以胰管内逆行注射牛磺胆酸钠法制作ANP模型.造模后24 h空肠插管分别灌注酪蛋白溶液(肠内营养组)和牛理盐水(埘照组和ANP组).每15 min收集胰液1次,共6次,记录胰液分泌量和检测胰液蛋白含量.取大鼠延髓孤束核,采用免疫组化法检测c-Fos蛋白表达.结果 ANP组和肠内营养组组内各时间段之间胰液分泌最无显著差别,两组相应时间段之间胰液分泌最也无显著差别,但均显著低于对照组对应时间段的胰液分泌量(P<0.05).对照组、ANP组和肠内营养组空肠灌注过程中胰液蛋白含量水平稳定,不同时间段间无明显差异,但ANP组和肠内营养组空肠灌注后0～15 min、15～30 min、30～45 min、75～90 min时间段内胰液蛋白含量均低于对照组(P<0.05).肠内营养组灌注后延髓孤束核c-Fos蛋白表达阳性,而埘照组和ANP组延髓孤束核c-Fos表达阴性.结论 空肠内酪蛋白灌注可促进延髓孤束核c-Fos表达,但不增加胰液分泌量和胰液蛋白含量.     

N-Acetylcysteine Improves Pancreatic Microcirculation and Alleviates the Severity of Acute Necrotizing Pancreatitis

Background/Aims

To investigate the beneficial effect of N-Acetylcysteine (NAC) on pancreatic microvascular perfusion in acute necrotizing pancreatitis (ANP).

Methods

Fifty-four rats were divided into a control group, an ANP group and an NAC-treated group. The ANP model was established by a retrograde injection of 3% sodium taurocholate into the pancreatic duct. The NAC-treated group received an intravenous infusion of NAC just 2 hours before and 30 minutes after the induction of ANP. The pancreatic microvascular perfusion was measured with laser Doppler flowmetry and pancreatic samples were collected for histological examination.

Results

The microvascular perfusion in the NAC-treated group decreased slightly and exhibited a significant increase compared to the ANP group (p<0.01). A pathological examination revealed that edema and inflammatory infiltration decreased, and the hemorrhaging and necrosis of the pancreas were significantly reduced.

Conclusions

NAC could improve pancreatic microvascular perfusion and alleviate the severity of sodium taurocholate-induced ANP, possibly representing a new therapeutic approach to prevent the progression of ANP.     

施他宁在急性坏死性胰腺炎治疗中的应用

目的:探讨施他宁在急性坏死性胰腺炎治疗中的作用。方法:1995年8月至1996年9月本院消化科共收治急性坏死性胰腺炎27例,其中24例用施他宁治疗,3例转外科手术治疗。结果:用施他宁保守治疗的24例患者中除2例死亡外均存活,存活率92％,转外科手术3例中2例死亡。结论:施他宁不失为一个治疗急性坏死性胰腺炎的良药,能大大地提高患者的存活率。     

急性坏死性胰腺炎治疗的临床分析

目的:对急性坏死性胰腺炎(ANP)的内、外科治疗进行临床分析。方法:对58例ANP进行了分析,其中非手术组15例,手术组43例。在治疗的以下几个方面进行了对比:在非手术组中是否使用胰液/胰酶抑制剂;在手术组中72小时内和72小时后手术;在抗生素治疗上,二联用药(头孢唑啉 甲硝唑)与多联用药。结果:非手术组中用过胰液分泌抑制剂或胰酶抑制剂者死亡率为12、5％,显著低于未用过胰液分泌抑制剂或胰酶抑制剂者(71.4％,P<0.05);手术组中72小时以内手术者死亡率为36.7％,显著低于72小时以上者(84.6％,P<0.01);抗生素治疗方面,二联用药(头孢唑啉 甲硝唑)与广谱、多联用药的死亡率无显著差异(P>0.05)。结论:由于胰液/胰酶抑制剂能降低轻症ANP的死亡率,轻症病人应积极采用胰液/胰酶抑制剂为主的综合治疗,重症病人应早期手术;而在抗生素治疗上,除非有严重感染,一般仅需二联用药,无需多种广谱抗生素联用。     

导向大黄素脂质体治疗急性出血坏死性胰腺炎的实验研究

本文报道用自制的大黄素脂质体在实验性出血坏死性胰腺炎(AHNP)的动物模型中作导向治疗的研究。实验依据是大黄素经丙谷胺和脂质体包裹后注入动脉,结果其在胰组织中的浓度显著高于单纯大黄素,大鼠在胆胰管内注射5％牛磺胆酸钠造成AHNP后,随机分为脂质体治疗组(PE组)、善得定治疗组(S组),大黄素治疗组(E组)和生理盐水对照组(Na组)。另外还设立了假手术组(P组)以及正常对照组。治疗均于造模后15min经腹主动脉给药。观察指标包括腹水、血清脂肪酶和淀粉酶、胰腺病理及死亡率。结果示治疗3小时后,各治疗组血清和腹水酶水平均较Na组有显著差异。6小时后PE组的酶水平较E组有显著差异。病理改变方面,PE组的病变亦明显较轻。死亡率的比较亦示PE组的效果最好(62.5％比87.5％)。本文讨论中提出PE治疗,特别是动脉内给药有明显效果,同时指出所用的脂质体制剂并未引起任何毒副作用,说明磷脂酶A,对胰腺细胞并无毒性反应。     

No Debridement Is Necessary for Symptomatic or Infected Acute Necrotizing Pancreatitis: Delayed, Mini-Retroperitoneal Drainage for Acute Necrotizing Pancreatitis Without Debridement and Irrigation

We sought to determine if necrosectomy can be omitted for complicated acute necrotizing pancreatitis (ANP). Since 1996, we prospectively performed retroperitoneal drainage by introducing a sump drain to the pancreatic head area via a small left flank incision without debridement and irrigation on 19 consecutive complicated ANP patients. We purposely delayed surgery until liquefaction of retroperitoneal tissue reached the left flank. Our patients had a mean Ranson’s and APACHE II score of 5.9 (range, 4–8) and 20.1(range, 4–45), respectively. Sixteen available CT showed retroperitoneal liquefaction after 21.3 days (range, 14–26). Operations were delayed for 4.7 weeks (range, 1.3–9.0). No patient succumbed during this period. The indications were infected necrosis in 16 and severe abdominal pain/food intolerance in 3 patients. Average skin incision was 4.0 cm (range, 3–9). Fungi or bacteria were cultured in 15 patients (80.0%). The recovery courses were surprisingly uneventful. Oral intake began within 2.4 days (range, 1–5) and mean hospital stay (16 survivals) was 23.2 days (range, 4–120) after operation. Drains were completely removed 120.6 days (range, 60–250) later from these outpatients. One gastric perforation and one minor duodenal leak were the only procedure-related complications (10.5%). Three patients died (15.8%), although one had a healed ANP. In conclusion, this delay-until-liquefaction strategy without necrosectomy is an easy and effective treatment method.     

Postoperative Acute Pulmonary Thromboembolism in Patients with Acute Necrotizing Pancreatitis with Special Reference to Apheresis Therapy

Abstract: Eight patients with pancreatic abscesses secondary to acute necrotizing pancreatitis underwent drainage of their abscesses under laparotomy. Two of them died of acute pulmonary thromboembolism (PTE) within 1 week. Autopsy revealed a large thrombus at the main trunk of the pulmonary artery and in the left common iliac vein. Femoral catheter insertion/indwelling, immobilization, surgery, increased trypsin/kinin/kallikrein, increased endotoxin, and decreased antithrombin-HI (AT-IH) were present following drainage of the pancreatic abscesses. With respect to the bedside diagnosis of acute PTE, alveolar-arterial oxygen gradients obtained by blood gas analysis and mean pulmonary artery pressure estimated by pulsed Doppler echocardiography are very useful. In terms of the treatment, attention should be paid to the following to prevent deep venous thrombosis: prophylactic administration of low molecular weight heparin and administration of AT-III (AT-III ≥ 80%), use of the subclavian vein whenever possible as blood access for apheresis therapy, as short a compression time as possible after removing the blood access catheter (≤ s 6 h), and application of intermittent pneumatic compression devices or elastic compression stockings on the lower extremities.     

前列腺素E_1冶疗急性水肿型胰腺炎疗效观察

为了解前列腺素E1(PGE1)治疗急性胰腺炎(AP)的疗效,将54例AP随机分为治疗组26例,对照组28例。两组除禁食、输液抗生素等相同外,治疗组用PGE1 200μg加5％葡萄糖液500ml静滴,每天1次,连用3天。同时观察腹痛及血、尿淀粉酶变化。结果表明:治疗组腹痛消失及血尿淀粉酶恢复至正常时间均较对照组明显缩短(P<0.01)。提示PGE1可提高AP疗效。     

西米替丁对急性胰腺炎的影响及机制探讨

目的:探讨西米替丁治疗急性胰腺炎的利弊及其机制。方法:对156例急性水肿型胰腺炎患者进行传统疗法与传统疗法加西米替丁的治疗对照研究,并检测了50例消化性溃疡患者服用西米替丁前后的血清胃泌素及24例急性胰腺炎患者急性发病期的血清胃泌素。结果西米替丁组腹痛消失时间、血尿淀粉酶下降时间、住院时间均较对照组明显延长。另有40.16％(51/127)的患者出现病情反复。溃疡病患者服用西米替丁后血清胃泌素明显升高。急性胰腺炎发病期血清胃泌素明显高于正常,发病当日超过正常值4～10余倍。结论:急性胰腺炎的发病可能与血清胃泌素过高有关,西米替丁虽能降低胃酸,但因反馈性升高血清胃泌素而不利于急性胰腺炎的恢复。     

The Penetration of Ciprofloxacin into Human Pancreatic and Peripancreatic Necroses in Acute Necrotizing Pancreatitis

Background: Antibiotic prophylaxis in necrotizing pancreatitis has recently gained acceptance. Published studies, however, used different antibiotic regimes and some antibiotics penetrated pancreatic tissue or pancreatic necroses only poorly. The aim of this study was to assess the penetration of ciprofloxacin (CIP) into necrotic pancreatic and peripancreatic tissue. Patients and Methods: Serum, pancreatic necroses, peripancreatic fat tissue necroses and infected omental fluid levels of CIP were measured after 51 operations in 14 patients. Results: The median penetration ratio of CIP was 137.5% (range 11–196%) in infected omental bursa fluid, 59.6% (3–214%) in pancreatic necroses and 67.1% (1–250%) in peripancreatic necroses. Chemotherapeutical ratios of CIP as a marker for antimicrobial potency were high against most relevant pathogens in necrotizing pancreatitis. Conclusion: Due to its antimicrobial spectrum and the good penetration into the relevant compartments, CIP may be useful in preventing local infection in necrotizing pancreatitis. Received: August 28, 2000 · Revision accepted: August 28, 2001