抗氧化剂对大鼠重症急性胰腺炎胰腺腺泡细胞凋亡的影响

目的探讨四氢化吡咯二硫代氨基甲酸酯（PDTC）对重症急性胰腺炎（SAP）胰腺腺泡细胞凋亡的影响。方法SD大鼠72只，随机分为：假手术组（sham operation，SO）、SAP组和PDTC组。SAP模型采用5％牛磺胆酸钠1ml/kg胰胆管逆行穿刺注射建立，PDTC组在造模前1h给予腹腔注射PDTC（1130mg/kg），术后分4个时段（1、3、6、12h）分批进行腹主动脉采血后处死，取胰腺组织作病理切片与液氮冻存。胰腺腺泡细胞的凋亡检测应用TUNEL法、电镜以及免疫组化法检测胰腺组织Caspase-3的表达；核因子（NF）-κB活化的检测应用免疫组化法。同时观察各组血清淀粉酶、脂肪酶水平及胰腺组织病理学评分。结果SAP组各时间点血清淀粉酶及脂肪酶水平及胰腺组织病理组织学评分较SO组显著增高（P〈0．05）。PDTC治疗组血清淀粉酶、脂肪酶水平较SAP组明显降低；胰腺组织病理组织学评分明显改善。PDTC治疗后3、6、12h胰腺组织Caspase-3的表达显著高于SAP组（P〈0．01），而在1h无统计学差异；各时间点胰腺腺泡细胞凋广指数显著高于SAP组（P〈0．01）；NF—κB的活化显著低于SAP组（P〈0．01）。结论SAP时，PDTC可能通过抑制NF—κB的活化，从而抑制NF—κB介导胰腺细胞的抗凋亡效应，减少胰腺腺泡细胞坏死。

Effectiveness of the antioxidant on apoptosis of pancreatic acinus cells in severe acute pancreatitis of rats

objective To observe the effectiveness of exogenous pyrrolidine dithiocarbamate (PDTC),an antioxidant,on apoptosis of pancreatic acinus cells in severe acute pancreatitis (SAP).Methods Seventy-two male Sprague-Dawley rats were randomly allocated into 3 groups:control group,SAP group and PDTC-treated group.SAP was induced by injection of 5% sterile sodium taurocholate into biliopancreatic duct at dose of 1ml/kg,while control group was only given sham operation.In treatement group,PDTC was administrated intraperitoneally 1 hour before the initiation of pancreatitis at the dose of 100 mg/kg.All the rats were sacrificed at 1,3,6,and 12 hours after the onset of operation.Apoptosis was studied by TUNEL and electron microscopy methods.The expression of activated Caspase-3 and NF-kB in pancreatic tissue were determined by immunohistochemistry.Besides,the serum level of amylase and lipase were examined,two pathologists assessed histological scoring for tissue independently.Results The levels of serum amylase and lipase as well as histological scoring were all significantly increased in SAP group (P<0.05,respectively vs.SO) at each time point,while serum levels of amylase and lipase as well as the histolog- ical score of pancreatitis improved after administration of PDTC.In PDTC-treated group,the expression level of Caspase-3 in pancreatic tissue was significantly increased than that of SAP group at 3,6 and 12 hours (P<0.01, vs.SAP),but there was no significant difference at 1 hour.Moreover,treated with PDTC markedly inhibited NF-kB activation and increased apoptosis index of pancreatic acinus cells (P<0.01,vs.SAP).Conclusion The result of this study indicated that admmistration of exogenous PDTC may attenuate the severity of SAP by inhibiting NF-kB activation and thus induced apoptosis of pancreatic acinus cells.