聚腺苷二磷酸核糖聚合酶抑制剂3-氨基苯甲酰胺对重症急性胰腺炎大鼠腺垂体损伤的保护作用

摘要

Objective To evaluate the protection of 3-aminobenzamide (3-AB),an inhibitor of Poly (ADP-ribose) polymerase (PARP),on severe acute pancreatitis associated adenohypophysis injury in rats.Method Forty Wistar rats were randomly divided into 4 groups:sham operation group (SO group,n=8),SAP group (n=12),3-AB pretreatment group (n =12),drug control group (n =8).The bilepancreatic duct was cannulated through the duodenum and SAP model was induced by a standardized pressure-controlled retrograde infusion of 5％ sodium taurocholate (0.1 ml/100 g) into the bile-pancreatic duct.In 3-AB group,3-AB (20 mg/kg) was administered via femoral vein 30 min prior to the operation;other procedures were identical to SAP group.In SO group,pancreas was flipped several times only.In drug control group,3-AB (20 mg/kg) was administered via femoral vein 30 min prior to the operation.Serum amylase,lipase were measured.Pancreas and pituitary tissue were taken for pathological examination under light microscope.PARP and NF-κB antibodies for adenohypophysis immunohistochemical stains.Adenohypophysis cell was observed under electronic microscope.Result Serum amylase,lipase and pancreas pathological scores were significantly higher in 3-AB group compared with SO group (P ＜ 0.05),but lower than that in SAP group (P ＜ 0.05).Adenohypophysis pathological injury was less severe in 3-AB group.Expressions of PARP and NF-κB in adenohypophysis cells were significantly higher in 3-AB group compared with SO group,but lower than that in SAP group (P ＜ 0.05).Ultrastructural change of thyrotroph cell was relieved in 3-AB group.No significant difference was observed between SO group and drug control group in PARP and NF-κB expression nor adenohypophysis pathological injury.Conclusions 3-AB exerts the protective effect against acute pancreatitis associated adenohypophysis injury by inhibition of PARP and NF-κB.%目的 探讨聚腺苷二磷酸核糖聚合酶抑制剂3-氨基苯甲酰胺(3-AB)对SAP大鼠腺垂体的保护作用.方法 雄性Wistar大鼠40只,随机分为4组:假手术组(SO组,n=8)、重症急性胰腺炎模型组(severe acute pancreatitis model group,SAP组,n=12),3-AB预处理组(3-AB组,n=12)和3-AB药物对照组(药物对照组,n=8).SAP组大鼠胆胰管逆行注射5％牛磺胆酸钠制备重症急性胰腺炎模型,3-AB组造模同SAP组,在造模前30 min股静脉注射3-AB(20 mg/kg),SO组仅翻动胰腺后关腹,药物对照组仅行股静脉注射3-AB(20 mg/kg),余同SO组.全自动生化仪检测各组血清淀粉酶及脂肪酶水平.HE染色观察各组胰腺组织及腺垂体病理改变.以PARP抗体及NF-KB抗体行腺垂体免疫组化染色,并对阳性表达行定量分析.电镜下观察腺垂体细胞超微结构改变.结果 与SO组相比,SAP组大鼠血淀粉酶、脂肪酶水平明显升高(P＜0.05),SAP组胰腺病理评分显著高于SO组(P＜0.05).3-AB组淀粉酶、脂肪酶及胰腺病理评分显著高于SO组(P＜0.05),但均较SAP组降低(P＜0.05).药物处理组上述指标与SO组无差别.SAP组腺垂体光镜下可见损伤严重,3-AB组光镜下腺垂体病理损伤较SAP组减轻.免疫组化示SAP组PARP及NF-KB在细胞核内高表达,3-AB组腺垂体PARP及NF-KB表达较SAP组显著降低(P＜0.05).电镜下可见3-AB组腺垂体细胞超微结构改变较SAP组减轻.光镜及电镜下,SO组和药物对照组均无明显改变.结论 3-AB可通过抑制PARP及下游NF-KB表达,对重症急性胰腺炎大鼠腺垂体损伤起保护作用.