【作者】 李强；

【导师】 苗毅； 刘训良；

【作者基本信息】 南京医科大学 ， 外科学， 2002， 硕士

【摘要】 目的：急性坏死性胰腺炎（ANP）是常见的急腹症，其病情演变迅速，并发症多，危害极大。随着人们生活水平的提高，发病率呈上升趋势。其发病机制尚未完全阐明，但胰酶原的异位异常激活引发胰腺炎已得到公认。目前临床尚缺乏特效方法阻止胰腺坏死的发生、发展。许多学者对其进行了长期不懈的研究，ANP的治疗策略也由过去常规手术为主趋向于以保守为主的“个体化方案”。近年来，针对ANP治疗的药物不断问世，为ANP的治疗提供了新的乎段。但这些药物的疗效不确切、费用昂贵，难以广泛使用。因此，经济有效药物的开发，显得尤为重要。本实验使用磷脂酶A₂（PLA₂）抑制剂氯丙嗪（Chlorpromazine,CPZ）对急性坏死性胰腺炎大鼠腹腔注射给药，观察其治疗效果，以期为临床治疗胰腺炎提供一个有效的药物。 材料和方法：健康雌性SD大鼠120只，取30只作为Ⅰ组，为对照组（NC组），其余90只随机分为Ⅱ、Ⅲ组，每组45只，Ⅱ组为胰腺炎组（ANP组），Ⅲ组为胰腺炎+氯丙嗪治疗组（CPZ组）。模型制备采用胰管注射法：Ⅱ、Ⅲ组按1ml／kg,0.2ml／min经十二指肠胰管内注射5％牛磺胆酸钠溶液，制成胰腺炎模型。Ⅰ组则经十二指肠胰管内注入等量生理盐水，为假手术组。Ⅱ组制模成功后即按0.25ml／100g剂量腹腔注射生理盐水，24、48小时重复。Ⅲ组则同法给予等量的0.4％氯丙嗪。三组动物分别于术后24、48、72小时无菌条件下活杀取材，腹主动脉取血，送检血淀粉酶（AMY）、磷脂酶A₂（PLA₂）、白介素-6（IL-6）。取胰腺、肺脏、肝脏、肾脏作普通病理切片，判断病变及损伤程度。 结果：1．Ⅰ、Ⅱ、Ⅲ两组大鼠术后存活率分别为100％、57.8％ 南京医科大学硕士学位论文 和 71o，治疗组明显高于胰腺炎组。2．11、Ill两组大鼠血清淀粉 酶术后均明显升高，随时间延长呈下降趋势，三个时段分别同对 照组比较，有显著性差异o＜0刀1)，11、111两组之间比较，也存 在着显著性差异（P＜0．05）。3．术后11、Ill两组动物血清凡A。较 对照组均明显升高，有显著性差异（P＜0刀5），两组之间比较， 11组较 Ill组数值高，三个时段差异均有显著性（P＜0．of）。4．术后 三个时段，随着时间延长，两组大鼠IL＊数值呈逐渐下降趋势。 胰腺炎组的IL6数值较对照组均明显升高，有显著性差异（P。 O刀1）；治疗组同胰腺炎组相比，1卜6数值低，有显著性差异（P＜ O刀1）；治疗组术后24小时同对照组比较，存在显著性差异（P＜ 0刀5），术后48、72小时，治疗组同对照组比较，无显著性差异 呼列刀5)。5．病理变化和组织损伤（1）大体标本所见：AN P组可 见胰腺本身均有较大面积的出血坏死，与周围组织粘连广泛。腹 腔内可见大量腹水，颜色暗淡或呈血性，各脏器表面色泽灰暗， 肠管扩张明显。肝脏、肺脏表面可见组织充血，偶有局灶性坏死 灶出现。治疗组腹水明显减少；钙化灶少量或不明显。胰腺本身 的出血坏死较制模成功时相比得到有效控制，未在进一步发展， 并且与周围组织粘连不明显。各脏器色泽基本正常或伴轻微充血。 以光镜所见：ANP组可见胰腺小叶大面积溶解性坏死，间质中大 面积脂肪空泡变性，少量残余正常组织。肺组织充血水肿，并可 见肺泡壁断裂等变化。肝脏可见变性坏死。治疗组胰腺、肺脏、 肝脏组织较ANP组明显减轻。（3）Sporma。评分提示：11、Ill两 组三个时段较对照组升高，差异有显著性（P＜0刀1），11、111两组 之间比较，有显著性差异呼＜0刀5)。 结论：急性坏死性胰腺炎时，氯丙嘻腹腔注射给药对其有一定 什台疗效果。使用该药为临床治疗胰腺炎提供了实验依据。更多还原

【Abstract】 Objective: Acute necrotizing pancreatitis (ANP) is a common surgical emergency with many complications. The pathogenesis of pancreatitis is not yet completely ascertainment. Abnormal ectopia enzyme activation is the key step for pancreas autodigestion. Until now there is no pathway for terminate or stop such autodigestion caused by avtivated enzyme. Recently, many drugs are applied to clinical, and provide many choices for treatment of pancreatitis. Unfortunately, there are too expensive but unreliable. So it is desire for both patient and doctor to find a effective and cheap drug. The aim of this study was to evaluate the feasiblity of chlorpromazine on treatment of acute necrotizing pancreatitis rats.Material and Methods: 120 healthy female SD rats were randomly divided into three groups: Group I normal control (NC group, n=30); Group II acute necrotizing pancreatitis (ANP group, n=45); Group III chlorpromazine treatment (ANP+CPZ group, n=45). ANP modle in group III and II was induced by the injection of 5% sodium taurocholate into pancreatic duct with the dosage of 1 ml/kg and rate of 0.2ml/min, group I was injected the equivalence saline with the same method as a control of sham operation. 0.4% Chlorpromazine was administered to group III Intraperitoneal with the dosage of 0.25ml/100g immediately after the model was made. The drug was supplied at 24h\ 48h repeatedly. Normal saline was given to Group IIin the same way and the same time. The animals were sacrificed at 24. 48. 72hour under sterile circumstance. The blood samples were collected for analysis of serum amylase(AMY). phospholipase A2 (PLA2). interleukin-6 (ⅠL-6). Pancreas, lung, liver and kidney were collected for pathologic examination. Spormann score was undertook for evaluation the damage of pancreas.Results: 1. The 72 hours survival rate was 100%. 71%. 57.8% in group Ⅰ . Ⅱ. Ⅲ respectively, that of group Ⅲ was higher than that in group Ⅱ. 2. Serum amylase in group Ⅱ and group Ⅲ increased highly and decreased gradually. The serum amylase level was lower in group Ⅲ than that in groupⅡ at 24. 48. 72h (P<0.05),but still above the normal control level (P<0.01). 3.The changes of PLA2 was similar to AMY. The PLA2 levels of group Ⅲ were lower than that of group Ⅱ (P<0.01). 4. ⅠL-6 increased highly in both groups. ⅠL-6 level decreased obviously in group Ⅲ when it was still higher in group Ⅱ. There was a significant difference between the two groups (P<0.05). 5. Pathologic changes: The structure of pancreas was almost normal in group Ⅰ . A large area necrosis and hemorrhage in pancreas was observed in the group Ⅱ, with a large amount of ascites and calcification spots. The normal pancreas was distributed sporadic. The surface of liver and lung was congestion, sometime necrosis could be observed. Compare in group Ⅱ , the pathologic changes of group Ⅲ were lighter. The Spormann score of group Ⅲ was lower than that in group Ⅱ (P<0.05).Conclusion: Chlorpromazine has shown therapeutic effects on treatment of ANP and it may provide a new feasible treatment approach for ANP.更多还原