选择性抑制环氧化酶-2（COX-2）可减少前列腺素E2的产生，并减轻实验性胰腺炎中的全身疾病后遗症。

Selective inhibition of cyclooxygenase-2 (COX-2) reduces prostaglandin E2 production and attenuates systemic disease sequelae in experimental pancreatitis.

作者信息

Foitzik Thomas, Hotz H G, Hotz B, Wittig F, Buhr Heinz J

机构信息

Department of Surgery, University of Rostock, Rostock, Germany.

出版信息

Hepatogastroenterology. 2003 Jul-Aug;50(52):1159-62.

PMID:12846004

Abstract

BACKGROUND/AIMS: Prostaglandins and prostaglandin-derived mediators play an important role in mediating the systemic inflammatory response in acute pancreatitis. COX (cyclooxygenase) is the key enzyme of prostaglandin synthesis. Whereas COX-1 produces prostaglandin mediators for physiological reactions, COX-2 is overexpressed in acute pancreatitis. The aim of this study was to investigate whether a selective COX-2 inhibitor alters prostaglandin production and attenuates systemic disease sequelae in severe acute pancreatitis in rats.

METHODOLOGY

Severe acute pancreatitis was induced in 36 rats by standardized intraductal infusion of bile salt and intravenous cerulein infusion. Six hours after acute pancreatitis induction, rats were randomized to receive either no COX inhibition (saline), nonselective COX inhibition by indomethacin (3 mg/kg, i.v.) or selective COX-2 inhibition by NS-398 (10 mg/kg, i.v.). Serum concentrations of prostaglandin E2 were measured before and after acute pancreatitis induction and 24 hrs after starting therapy. Routine cardiorespiratory and renal parameters were monitored to assess organ function.

RESULTS

Animals treated with the selective COX-2 inhibitor had significantly lower prostaglandin E2 values (211 +/- 17 vs. 366 +/- 37 and 435 +/- 13 pg/mL), produced more urine (18 +/- 4 vs. 13 +/- 3 and 12 +/- 3 mL/6-24 h) and had significantly fewer episodes of respiratory distress (defined as a pO2 < 80 mmHg or pCO2 > 50 mmHg for > 15 min; 12 vs. 57 and 71%) during the observation period than animals without or with nonselective COX inhibition.

CONCLUSIONS

Selective inhibition of COX-2 reduces prostaglandin E2 serum levels in this model of acute pancreatitis. This together with improved renal and respiratory function suggests an attenuation of the systemic response to pancreatic injury. COX-2 inhibition may be another step toward optimizing therapy in severe acute pancreatitis.

摘要

背景/目的：前列腺素及前列腺素衍生介质在介导急性胰腺炎的全身炎症反应中起重要作用。环氧化酶（COX）是前列腺素合成的关键酶。COX - 1产生用于生理反应的前列腺素介质，而COX - 2在急性胰腺炎中过度表达。本研究的目的是探讨选择性COX - 2抑制剂是否能改变前列腺素的产生，并减轻大鼠重症急性胰腺炎的全身疾病后遗症。

方法

通过标准化的胆管内输注胆盐和静脉注射蛙皮素，在36只大鼠中诱导重症急性胰腺炎。急性胰腺炎诱导6小时后，将大鼠随机分为三组，分别接受无COX抑制（生理盐水）、吲哚美辛非选择性COX抑制（3 mg/kg，静脉注射）或NS - 398选择性COX - 2抑制（10 mg/kg，静脉注射）。在急性胰腺炎诱导前后及开始治疗24小时后，测定血清前列腺素E2浓度。监测常规心肺和肾脏参数以评估器官功能。

结果

接受选择性COX - 2抑制剂治疗的动物前列腺素E2值显著降低（211±17 vs. 366±37和435±13 pg/mL），尿量增多（18±4 vs. 13±3和12±3 mL/6 - 24小时），并且在观察期内呼吸窘迫发作次数显著减少（定义为动脉血氧分压<80 mmHg或动脉血二氧化碳分压>50 mmHg持续超过15分钟；12次 vs. 57次和71%），而未接受或接受非选择性COX抑制的动物则不然。