不同剂量Apocynin对重症急性胰腺炎模型大鼠肠组织的保护作用

The protective effects of different doses of apocynin on intestines of rats with severe acute pancreatitis

目的探讨还原型辅酶Ⅱ氧化酶(NOX)抑制剂apocynin对重症急性胰腺炎(SAP)模型大鼠肠道损伤的保护作用及剂量关系。方法 53只SPF级Wistar大鼠随机分为假手术组(SO组,10只)、SAP模型组(SAP组,12只)、apocynin低剂量组(25 mg/kg,11只)、中剂量组(50 mg/kg,10只)、高剂量组(100 mg/kg,10只)。胆胰管逆行注射5%牛磺胆酸钠溶液制备SAP模型,造模前30 min,各剂量组注射apocynin干预。造模后12 h记录大鼠存活情况,测定各组腹水量、血清淀粉酶(AMY)、丙氨酸转氨酶(ALT)和肌酐(Cr)水平,并取胰腺、回肠组织行HE染色,进行组织病理学分析。结果 SAP组死亡2只,apocynin低剂量组死亡1只。SAP组大鼠腹水量、AMY、ALT、Cr水平、胰腺病理评分、回肠病理分级均较SO组明显升高(P<0.05)。低剂量组Cr、肠病理分级较SAP组降低,其他指标与SAP组比较差异无统计学意义。中、高剂量组腹水量、AMY、Cr、胰腺病理评分、肠病理分级均较SAP组降低(P<0.05)。高剂量组ALT、Cr水平较中剂量组升高(P<0.05)。结论 Apocynin可改善SAP模型大鼠症状并减轻肠损伤,这可能与其抑制NOX活性有关,50 mg/kg可能是最佳剂量。

Objective To investigate the optimal dose of apocynin to protect severe acute pancreatitis (SAP) and SAP caused intestinal injury in rats. Methods A total of 53 SPF male Wistar rats were randomly allocated into five groups: sham operation group (SO group, n=10), SAP group (n=12), low-dose apocynin group (25 mg/kg,n=11), medium-dose apocynin group (50 mg/kg,n=10) and high-dose apocynin group (100 mg/kg,n=10). SAP model was prepared by retrograde infusing 5% sodium taurocholate(1 mL/kg) into biliopancreatic duct of rat. At thirty minutes before modeling, apocynin was injected into rat to intervention. Thesurvival condition was recorded at 12 h after modeling, and blood samples were obtained for detecting serum amylase (AMY),alanine aminotransferase (ALT) and creatinine (Cr). Pancreatic and ileal tissue samples were obtained for HE staining andpathological examination. Results Two rats died in SAP group and one died in low-dose apocynin group. The quantity of ascites,the levels of AMY, ALT, Cr and pancreatic and intestinal pathologic scores were significantly increased in SAP group than thosein SO group (P < 0.05). Except the levels of Cr and intestinal pathologic score, there was no significant difference between lowdoseapocynin group and SAP group. The quantity of ascites ascites, levels of AMY, Cr and pancreatic and intestinal pathologicscores were significantly lower in medium-dose and high-dose apocynin groups than those in SAP group (P < 0.05). The levelsof ALT and Cr were significantly higher in high-dose apocynin group than those of medium-dose apocynin group (P < 0.05).Conclusion Apocynin improves SAP symptoms and reduces SAP caused intestinal injury in rats, which may be related to the inhibition of NOX activity, and 50 mg/kg of apocynin is the optimal dose