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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1 ml/kg 胰胆管逆行穿刺注射建立,PDTC 组在造模前1 h 给予腹腔注射PDTC(100 mg/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)-kB 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计分较 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、12 h 胰腺组织 Caspase-3的表达显著高于 SAP 组(P<0.01),而在1 h无统计学差异;各时间点胰腺腺泡细胞凋亡指数显著高下 SAP 组(P<0.01);NF-kB 的活化显著低于SAP 组(P<0.01)。结论 SAP 时,PDTC 可能通过抑制 NF-kB 的活化,从而抑制 NF-kB 介导胰腺细胞的抗凋亡效应,减少胰腺腺泡细胞坏死。
Objective To investigate the effect of pyrrolidine dithiocarbamate (PDTC) on pancreatic acinar cell apoptosis in severe acute pancreatitis (SAP). Methods Seventy two SD rats were randomly divided into sham operation (SO), SAP group and PDTC group. The SAP model was established by retrograde injection of 5% sodium taurocholate (1 ml / kg) into the pancreaticobiliary duct. PDTC (100 mg / kg) was intraperitoneal injected into the PDTC group 1 hour before the operation. , 6,12h) were sacrificed abdominal blood aorta after sacrifice, take the pancreatic tissue for pathological sections and liquid nitrogen cryopreservation. The apoptosis of pancreatic acinar cells detected by TUNEL method, electron microscopy and immunohistochemical detection of pancreatic tissue Caspase-3 expression; nuclear factor (NF) -kB activation detected by immunohistochemistry. At the same time, the serum amylase, lipase levels and pancreatic histopathological score were observed. Results The levels of serum amylase and lipase and the histopathological score of pancreas in SAP group were significantly higher than those in SO group at each time point (P <0.05). PDTC treatment group serum amylase, lipase levels were significantly lower than the SAP group; pancreatic histopathological score improved significantly. The expression of Caspase-3 in pancreatic tissue at 3, 6 and 12 h after PDTC treatment was significantly higher than that in SAP group (P <0.01), but not statistically significant at 1 h after PDTC treatment. The apoptosis index of pancreatic acinar cell was significantly higher at each time point Group (P <0.01). The activation of NF-kB was significantly lower than that of SAP group (P <0.01). Conclusions PDTC may inhibit NF-kB-mediated anti-apoptotic effect of pancreatic cells and reduce pancreatic acinar necrosis by inhibiting the activation of NF-κB.