摘要
目的探讨吡咯烷二硫代氨基甲酸酯(PDTC)对二甲基亚硝胺(DMN)所致肝纤维化大鼠肝组织中核转录因子-κB(NF-κB)表达的影响及其意义。方法雄性SD大鼠38只,随机分为正常对照组、DMN模型组和PDTC抑制组,DMN模型组和PDTC抑制组再各自随机分为2周及4周组,并腹腔注射DMN诱导大鼠肝纤维化模型,PDTC抑制组造模同时给予PDTC灌胃。应用化学发光凝胶电泳迁移率实验法检测肝组织NF-κB p65活性;采用实时定量聚合酶链反应法检测肝组织NF-κB p65 mRNA的表达;行苏木精-伊红染色光镜观察肝组织形态学改变;胶原纤维染色比较各组胶原面积。结果 DMN模型组和PDTC抑制组NF-κB p65活性及其mRNA表达均显著高于正常对照组(P<0.01),且随着时间的延长,4周组高于2周组(P<0.01,0.05)。与正常对照组比较,DMN模型组和PDTC抑制组均可见肝细胞炎症及明显胶原染色(P<0.01),且随着时间的延长,4周组肝细胞炎症及胶原染色强度重于或高于2周组(P<0.01,0.05)。同期比较PDTC抑制组在2周及4周时NF-κB p65活性及其mRNA表达均显著低于DMN模型组(P<0.01,0.05),胶原面积亦小于DMN模型组(P<0.01,0.05)。NF-κB p65活性、NF-κB p65 mRNA表达与大鼠肝组织胶原面积三者间呈正相关(r=0.747,0.658,0.844,P<0.01)。结论 NF-κB与大鼠肝纤维化密切相关;PDTC可能通过抑制NF-κB活性及其mRNA表达产生抗肝纤维化作用。
Objective To investigate the effect of pyrrolidine dithiocarbamate（PDTC）on the expression of nuclear factor-κB（NF-κB）in rats with liver fibrosis induced by dimethylnitrosamine（DMN）and its significance.Methods Thirty-eight male Sprague-Dawley rats were randomly divided into three groups ：normal control group,DMN model group and PDTC inhibition group.DMN model group and PDTC inhibition group were randomly classified into 2 weeks and 4 weeks groups,which were injected intraperitoneally with DMN to establish model of rat liver fibrosis for 2 or 4 weeks.The rats in PDTC inhibition group were treated with PDTC by intragastric administration.The activity of NF-κB p65 in liver tissues was detected by chemiluminescence electrophoretic mobility shift assay.The expression of NF-κB p65 mRNA was detected by real-time polymerase chain reaction.Hematoxylin-eosin staining was used to observe the morphology change and collagen fiber staining was used to compare the collagen area among the groups.Results The activity of NF-κB p65 and the expression of NF-κB p65 mRNA in liver tissues of DMN model group and PDTC inhibition group were higher significantly than those of normal control group（P〈0.01）,and with the time going on,they were higher significantly in 4 weeks group than those in 2 weeks group（P〈0.01,0.05）.Compared with normal control group,the hepatocytes inflammation and collagen fiber staining intensity were more significant（P〈0.01）,and with the time going on,the hepatocytes inflammation and collagen fiber staining intensity in 4 weeks were more significant than those in 2 weeks（P〈0.01,0.05）.The activity of NF-κB p65,the expression of NF-κB p65 mRNA and the collagen area in PDTC inhibition group were lower or less significantly than those in DMN model group at 2 or 4 weeks（P〈0.01,0.05）.There were positive relationship among the activity of NF-κB p65,the expression of NF-κB p65 mRNA and the collagen area in hepatic tissue（r=0.747,0.658,0.844,respectively,P〈0.01）.Conclusion NF-κB makes an important role in the course of liver fibrosis in rats.PDTC might prevent the hepatic fibrosis by suppressing the activity of NF-κB and diminishing the expression of NF-κB.
出处
《新乡医学院学报》
CAS
2013年第4期251-255,共5页
Journal of Xinxiang Medical University
基金
河南省教育厅自然科学研究计划项目(编号:200733001)
