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

摘要： 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。

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

Abstract： 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. The survival 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 and pathological 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 those in SO group (P < 0.05). Except the levels of Cr and intestinal pathologic score, there was no significant difference between low- dose apocynin group and SAP group. The quantity of ascites ascites, levels of AMY, Cr and pancreatic and intestinal pathologic scores were significantly lower in medium-dose and high-dose apocynin groups than those in SAP group (P < 0.05). The levels of 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.