Wang Yi Lin, Zheng Yun Jiang, Zhang Zi Ping, Su Jing Ying, Lei Ruo Qing, Tang Yao Qing, Zhang Sheng Dao
Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
J Dig Dis. 2009 Feb;10(1):30-40. doi: 10.1111/j.1751-2980.2008.00360.x.
To study the effects of gut-derived endotoxin translocation and NF-kappaB activation on the aggravating mechanism of severe acute pancreatitis (SAP) and of treatment with pyrrolidine dithiocarbamate (PDTC) on rats with SAP.
SD rats were randomly divided into sham operation group (SO), SAP group, SAP + lipopolysaccharide(LPS) group, pyrrolidine dithiocarbamate (PDTC) treatment group and LPS group. Biochemical parameters and cytokines were examined in the serum. Multiple organs pathological slices were examined. Expression of NF-kappaB mRNA in the liver tissue was detected by RT-PCR. Activation of NF-kappaB by the method of streptomycin avidin-peroxidase (SP) and expression of NF-kappaB p65 protein and its binding activity were analyzed by Western blot and electrophoretic mobidity shift assay (EMSA).
Compared with sham operation group, the concentration of TNF-alpha, alanine aminotransferase (ALT), and diamine oxidase (DAO) in serum significantly increased in SAP + LPS group (P < 0.05). Pathological changes were markedly observed in tissues and the expression of NF-kappaB mRNA in the liver significantly increased (P < 0.05) also, the activation of NF-kappaB and binding activity of NF-kappaB p65 protein in the liver markedly increased (P < 0.01) in SAP + LPS group. Treatment with PDTC markedly reduced concentration of ALT, DAO and TNF-alpha, and the expression of NF-kappaB, and the pathologic scores, as well as significantly decreased the expression of NF-kappaB p65 protein.
The activation and overexpression of NF-kappaB may participate in the aggravating mechanism of SAP. Treatment with PDTC has a protective effect on multiple organs damage in SAP.
研究肠道源性内毒素移位及核因子-κB（NF-κB）激活在重症急性胰腺炎（SAP）病情加重机制中的作用，以及吡咯烷二硫代氨基甲酸盐（PDTC）对SAP大鼠的治疗作用。
将SD大鼠随机分为假手术组（SO）、SAP组、SAP+脂多糖（LPS）组、PDTC治疗组和LPS组。检测血清中的生化参数和细胞因子。检查多个器官的病理切片。采用逆转录-聚合酶链反应（RT-PCR）检测肝组织中NF-κB mRNA的表达。采用链霉亲和素-过氧化物酶（SP）法分析NF-κB的激活情况，并用蛋白质免疫印迹法（Western blot）和电泳迁移率变动分析（EMSA）检测NF-κB p65蛋白的表达及其结合活性。
与假手术组相比，SAP+LPS组血清中肿瘤坏死因子-α（TNF-α）、丙氨酸氨基转移酶（ALT）和二胺氧化酶（DAO）的浓度显著升高（P<0.05）。组织中可见明显的病理变化，肝组织中NF-κB mRNA的表达也显著增加（P<0.05），SAP+LPS组肝组织中NF-κB的激活及NF-κB p65蛋白的结合活性显著增强（P<0.01）。PDTC治疗可显著降低ALT、DAO和TNF-α的浓度，以及NF-κB的表达和病理评分，并显著降低NF-κB p65蛋白的表达。
NF-κB的激活和过度表达可能参与了SAP的病情加重机制。PDTC治疗对SAP多器官损伤具有保护作用。
