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机构地区:[1]北京大学第九临床医学院北京世纪坛医院普外科, 100038 [2]首都医科大学宣武医院普外科
出 处:《中华普通外科杂志》2009年第11期904-907,共4页Chinese Journal of General Surgery
摘 要:目的探讨急性坏死性胰腺炎(ANP)胰腺损伤与核因子-κB(NF-κB)活化、胰腺细胞凋亡的关系及N-乙酰半胱氨酸(NAC)对胰腺损伤的影响。方法33只wistar大鼠分为正常对照、盐水对照和胰腺炎组。以3.5%牛磺胆酸钠逆行注入胰胆管制作ANP模型,于造模前、后1h应用NAC,12h后取材,采用凝胶电泳迁移率实验测定胰腺组织NF-κB活性、改良TUNEL法检测细胞凋亡。同时观察血淀粉酶、脂肪酶、胰腺组织湿/干重比率及病理改变:结果盐水对照组NF-κB活性很低(2.00±0.33),胰腺炎组NF-κB明显活化(6.03±0.41),造模前使用NAC抑制NF-κB活性(3.28±0.42),降低淀粉酶及胰腺湿/干重比率,促进胰腺细胞凋亡(P〈0.05)。NF-κB活化与凋亡呈负相关(r=-0.96,P〈0.01),与胰腺损伤病理呈正相关(r=0.63,P〈0.01);胰腺损伤病理分级与凋亡呈负相关(r=-0.98,P〈0.01)。结论NAC可能通过抑制胰腺NF-κB活化、促进胰腺细胞凋亡,减轻胰腺损伤。Objective To investigate the correlation between pancreatic nuclear faetor-κB (NF-κB) activation, cell apoptosis and pancreatic injury. To determine effects of N-acetylcysteine (NAC) on pancreatic injury in rats with acute neerofizlng pancreatitis (ANP). Methods Thirty-three Wistar rats were divided into five groups: normal group, normal saline (NS) group, ANP group, prophylactic and therapeutic groups with NAC randomly. ANP was produced by 3.5% sodium taurocholate retrograde injection. In the prophylactic group, rats received intravenous (i. v. ) injection of NAC (300 mg/kg) 1 hour before tauroeholate injection and in the therapeutic group, NAC i. v. injection was given 1 hour after sodium tauroeholate injection. Animals were sacrificed at 12 hours after induction of pancreatitls. Activation of NF-κB in pancreatic tissues was determined by electrophoretic mobility shift assay(EMSA). Cell apoptosis was assessed by modified TUNEL method. The following parameters were also measured: plasma levels of amylase and lipase, pancreatic wet/dry weight ratio and bistologic grading. Results Taarocholate pancreatitis is characteristic of necrosis, haemmThage, and sexere leukocyte infiltration in the pancreas. Plasma amylase and lipase levels, pancreatic wet/dry weight ratio increased in rats of ANP. NF-κB banding activity was higher after pancreatitis induction (6.03±0. 41 ). When NAC was given 1 hour before induction of pancreatitis, the activation (3.28 ± 0. 42) of NF-κB was prevented with significantly decreased severity of pancreatitis as assessed by amylase, pancreatic wet/dry weight ratio. The number of apoptotic cells in pancreatic tissue sections was greater in rats treated with NAC than in rats not treated with NAC. There was a negative correlation between NF-κB banding activity and apoptosis of pancreatic cells ( r = - 0. 96, P 〈 0. 01 ) and there was a positive correlation between NF-κB activation and histopathological score ( r = 0. 63, P 〈0. 01 ). His
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