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目的探讨塞来昔布调节氧调节蛋白150(Oxygen Regulated Protein-150,ORP-150)对重症急性胰腺炎(severe acute pancreatitis,SAP)大鼠保护作用的最佳剂量。方法 30只Wistar大鼠随机分为5组,假手术组(SO组)、SAP组、塞来昔布低剂量组(5 mg/kg)、塞来昔布中剂量组(10 mg/kg)、塞来昔布高剂量组(20 mg/kg)。胆胰管逆行注射5%牛磺胆酸钠制备SAP模型,术后3 h剖杀大鼠,分别测定各组腹水量、血清淀粉酶(AMY)、丙氨酸转氨酶(ALT)值和肌酐(Cr)值,并取胰腺组织行病理学检查。结果 SAP组腹水量、AMY、ALT值、Cr值、胰腺病理评分值均较SO组显著升高(P<0.05)。中剂量和高剂量组腹水量、AMY、胰腺病理评分值较SAP组显著降低(P<0.05),而低剂量组上述指标较SAP组改变差异无统计学意义(P>0.05)。高剂量和中剂量组术后腹水量、AMY、胰腺病理评分较低剂量组显著降低(P<0.05),高剂量组与中剂量组间上述指标差异无统计学意义(P>0.05);在肝肾功能的指标检测上,高剂量组较中剂量和低剂量组ALT值显著升高(P<0.05)。SO组ORP-150表达较低,SAP组表达较高,塞来昔布低剂量组几乎不表达,中剂量组表达最高,高剂量组较中剂量组表达下降。结论塞来昔布是通过调节ORP-150的表达改善SAP大鼠症状,并且以中剂量(10 mg/kg)效果最佳。
Objective To investigate the optimal dose of celecoxib regulating the protective effect of Oxygen Regulated Protein-150 (ORP-150) on rats with severe acute pancreatitis (SAP). Methods Thirty Wistar rats were randomly divided into 5 groups: sham operation group (SO group), SAP group, celecoxib low dose group (5 mg / kg), celecoxib medium dose group (10 mg / kg) , Celecoxib high-dose group (20 mg / kg). The pancreatic duct was retrogradely injected with 5% sodium taurocholate to prepare SAP model. The rats were sacrificed at 3 h after operation, and the levels of ascites, serum amylase (AMY), alanine aminotransferase (ALT) and creatinine Cr) value, and take pancreatic tissue pathological examination. Results Ascites, AMY, ALT, Cr, and pancreatic pathological score in SAP group were significantly higher than those in SO group (P <0.05). The amount of ascites, AMY and pancreatic pathological score in middle and high dose groups were significantly lower than those in SAP group (P <0.05), while those in low dose group were not significantly different from those in SAP group (P> 0.05). The ascites volume, AMY and pancreatic pathology score of high and middle dose groups were significantly lower than those of lower dose group (P <0.05), but there was no significant difference between high dose group and middle dose group (P> 0.05) The indicators of liver and kidney function detection, high-dose group than the medium and low dose ALT value was significantly increased (P <0.05). The expression of ORP-150 was lower in SO group, higher in SAP group, less in celecoxib low dose group, highest in middle dose group and lower in middle dose group than that of middle dose group. Conclusion Celecoxib improved the symptoms of SAP rats by regulating the expression of ORP-150, and the best dose was 10 mg / kg.