核因子-κB反义寡核苷酸对肝纤维化小鼠肝组织核因子-κB活性和病理改变的影响  

NF-κB activity and pathologic changes in mice with hepatic fibrosis after treated with NF-κB antisense oligonucleotide

作　　者：周宇[1] 刘荣火[1] 叶石才[1] 王皓[1] 冯晓[1] 魏国丽[1] 包仕廷[2] 唐志凌[1] 陈科全[1] 祝斌[1] 

机构地区：[1]广东医学院附属医院消化科,湛江524001 [2]广东医学院附属医院肝胆外科,湛江524001

出　　处：《中华实验外科杂志》2009年第12期1645-1647,共3页Chinese Journal of Experimental Surgery

基　　金：广东省自然科学基金资助项目（04011392）

摘　　要：目的应用核因子（NF）-κB反义寡核苷酸（ASON）治疗肝纤维化小鼠模型，观察NF-κBp65ASON对小鼠肝组织NF-κB活性和肝纤维化程度的影响，探讨NF-κBp65ASON治疗肝纤维化的可能机制。方法实验小鼠分组：正常组（8只）、肝纤维化模型组（8只）、反义寡核苷酸（NF-κBp65ASON）治疗组（8只）、正义寡核苷酸（SON）治疗组（8只）、错义寡核苷酸（MSON）治疗组（8只）、NF-κBp65ASON对照组（8只）、SON对照组（8只）和MSON对照组（8只）；采用凝胶迁移率变动分析（EMSA）检测NF-κBDNA结合活性；病理切片（Masson染色）评价肝纤维化小鼠模型肝纤维化程度。结果NF-κBp65ASON治疗组小鼠肝组织NF-κB活性（12411．75±502．78）、肝纤维化病理积分（1．13±0．64）比模型组（16346．88±449．05、2．88±0．64）明显降低，差异有统计学意义（P〈0．01）。SON治疗组（16460．38±575．26、2．75±1．17）和MSON治疗组（15959．25±746．27、3．00±0．53）的NF-KB活性、肝纤维化病理积分与模型组比较差异无统计学意义（P〉0．01）。结论NF-κBp65ASON能显著抑制小鼠肝组织的NF-κB活性，降低肝纤维化程度。Objective To observe the effects of nuclear factor-κB antisense oligonucleotide （ NF-κB p65 ASON） on NF-κB activity and hepatic fibrosis in liver tissues of mice with hepatic fibrosis, and study the possible mechanism of NF-κB p65 ASON treating hepatic fibrosis. Methods A total of 64 BALB/c mice were divided into normal group, model group, NF-κB p65 ASON-treated group, sense ohgonucleotide （SON）-treated group, missense oligonucleotide （MSON）-treated group, control group of NF-κB p65 ASON, control group of SON and control group of MSON （n = 8 each）. Gel mobility shift assay （EMSA） was used to detect the DNA binding activity of NF-κB. Masson staining was used to observe the degree of hepatic fibrosis. Results The treatment of NF-κB p65 ASON could lower the NF-κB activity （12 411.75±502.78 ）, and fibrosis pathological scores （1. 13± 0.64 ）. As compared with model group （ 16 346.88± 449.05,2.88 ±0.64） ,there was significant difference （ P 〈0.01 ）. But there was no significant change in both SON-treated group （16 460.38 ±575.26,2.75±1. 17） and MSON-treated group （15 959.25±746.27,3.00±0.53 ） as compared with modal group in the NF-κB activity, and fibrosis pathological scores （P 〉 0.01 ）. Conclusion NF-κB p65 ASON can inhibit the NF-κB activity of the mice with hepatic fibrosis efficiently, and lessen the severity of hepatic fibrosis.

关 键 词：肝纤维化 核因子-ΚB 反义寡核苷酸 病理学 

分 类 号：R575.2[医药卫生—消化系统]