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别嘌醇在实验性急性坏死性胰腺炎中的作用。

The role of allopurinol in experimental acute necrotizing pancreatitis.

作者信息

Isik A Turan, Mas M Refik, Yamanel Levent, Aydin Sezai, Comert Bilgin, Akay Cemal, Erdem Gokhan, Mas Nuket

机构信息

Department of Internal Medicine, Gulhane School of Medicine, Baskent University, Ankara, Turkey.

出版信息

Indian J Med Res. 2006 Dec;124(6):709-14.

Abstract

BACKGROUND & OBJECTIVES: Acute pancreatitis (AP) in its severe form can lead to severe complications and death. Translocation of bacteria from the gut is one of the most important factors in the development of septic complications and mortality in acute pancreatitis. Oxygen-derived free radicals have been suggested to play a major role in the pathogenesis of AP. Xanthine oxidase enzyme is an important source of reactive oxygen metabolites. We undertook this study to evaluate the effect of allopurinol on bacterial translocation, oxidative stress and the course of AP in a rat model.

METHODS

Male Sprague-Dawley rats (n=48) were randomly allocated into three equal groups. Acute pancreatitis (AP) was induced in group II (AP+Saline), and group III (AP+allopurinol) by retrograde infusion of taurocholate into the common biliopancreatic duct. Group I rats (Sham) received normal saline infusion into the common biliopancreatic duct for mimicking pressure effect. Group III rats were treated with allopurinol intraperitoneally for 48 h after induction of pancreatitis. Blood samples were drawn from all animals for biochemical analyses and pancreatic tissues were examined for bacterial translocation.

RESULTS

Acute pancreatitis was developed in all groups, but not in group I (Sham), as indicated by microscopic parenchymal necrosis, fat necrosis and abundant turbid peritoneal fluid. Pathologic score of the pancreatitis in the allopurinol group (14.0 +/- 0.5) was lower when compared with group II (19.2 +/- 0.6) (P<0.001). Bacterial translocation to pancreas in group treated with allopurinol was significantly lower when compared with control group (p<0.02). Plasma glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) levels were higher and malondialdehyde (MDA) levels were lower in allopurinol group when compared with those in control groups.

INTERPRETATION & CONCLUSION: Our findings suggested that addition of allopurinol to the treatment protocol in the acute pancreatitis might improve the pathologic score, bacterial translocation and oxidative stress parameters. However, more studies need to be done to confirm these findings.

摘要

背景与目的

重症急性胰腺炎(AP)可导致严重并发症及死亡。肠道细菌移位是急性胰腺炎发生脓毒症并发症及死亡的最重要因素之一。有研究表明氧自由基在急性胰腺炎发病机制中起主要作用。黄嘌呤氧化酶是活性氧代谢产物的重要来源。我们进行本研究以评估别嘌呤醇对大鼠急性胰腺炎模型中细菌移位、氧化应激及病程的影响。

方法

将48只雄性Sprague-Dawley大鼠随机分为三组。通过向胆胰管逆行注入牛磺胆酸盐,在第二组(AP+生理盐水组)和第三组(AP+别嘌呤醇组)诱导急性胰腺炎。第一组大鼠(假手术组)向胆胰管注入生理盐水以模拟压力效应。第三组大鼠在胰腺炎诱导后腹腔注射别嘌呤醇48小时。采集所有动物的血样进行生化分析,并检查胰腺组织的细菌移位情况。

结果

所有组均发生了急性胰腺炎,但第一组(假手术组)未发生,表现为显微镜下实质坏死、脂肪坏死及大量浑浊的腹腔积液。别嘌呤醇组胰腺炎的病理评分(14.0±0.5)低于第二组(19.2±0.6)(P<0.001)。与对照组相比,别嘌呤醇治疗组胰腺的细菌移位明显减少(p<0.02)。与对照组相比,别嘌呤醇组血浆谷胱甘肽过氧化物酶(GSH-Px)和超氧化物歧化酶(SOD)水平较高,丙二醛(MDA)水平较低。

解读与结论

我们的研究结果表明,在急性胰腺炎治疗方案中加用别嘌呤醇可能改善病理评分、细菌移位及氧化应激参数。然而,需要更多研究来证实这些发现。

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