核因子κB/生存素信号通路在大鼠颈动脉球囊损伤模型内膜增生中的作用  

Role of NF-κB/survivin signal pathway on intima hyperplasia of rat carotid balloon injury restenosis model

作　　者：成威[1] 邓长金[1] 金露萍[1] 邵玲[1] 徐晓东[1] 舒春明[1] 

机构地区：[1]荆门市第一人民医院心内科,448000

出　　处：《中华心血管病杂志》2015年第3期248-253,共6页Chinese Journal of Cardiology

基　　金：湖北省自然科学基金（2010CDB03601）

摘　　要：目的 探讨核因子κB/生存素信号通路在大鼠颈动脉球囊损伤模型内膜增生中的作用.方法 构建核因子κB siRNA慢病毒载体（滴度1×108 TU/ml）,并在33只SD大鼠中建立颈动脉球囊损伤模型.建模后将SD大鼠分为阴性对照组（n=11）、核因子κB siRNA转染组（n=11）和核因子κB siRNA转染＋YM155（生存素抑制剂）组（n=11）,同时以损伤对侧的正常颈动脉作为正常对照组（n=11）.7d后各组分别处死5只SD大鼠并取材,以RT-PCR检测核因子κB及生存素mRNA水平.28 d后各组分别处死6只SD大鼠并取材,苏木精-伊红染色后比较内膜增生程度,以免疫组织化学法检测内膜增殖细胞核抗原（PCNA）及中膜α-SM-actin的表达.结果 （1）术后7d,阴性对照组核因子κB及生存素mRNA水平均高于正常对照组（P均＜0.05）;核因子κB siRNA转染组核因子κB mRNA水平低于阴性对照组（P＜0.05）,而与核因子κB siRNA转染＋YM155组比较差异无统计学意义（P＞0.05）;核因子κB siRNA转染组生存素mRNA水平低于阴性对照组（P＜0.05）,而高于核因子κB siRNA转染＋YM155组（P＜0.05）.（2）术后28 d,与正常对照组比较其余3组均有不同程度的内膜增生.阴性对照组、核因子κB siRNA转染组、核因子κB siRNA转染＋YM155组中膜面积差异无统计学意义（P＞0.05）.阴性对照组、核因子κB siRNA转染组、核因子κB siRNA转染＋YM155组的内膜面积分别为（0.13 ±0.01）、（0.11 ±0.01）和（0.09 ±0.01）mm2,各组间差异均有统计学意义（P均＜0.05）;内膜面积/中膜面积分别为1.55±0.07、0.92 ±0.08和0.76±0.06,各组间差异均有统计学意义（P均＜0.05）;剩余狭窄率分别为（58.71±0.02）、（32.13±0.05）和（26.42±0.03）％,各组间差异均有统计学意义（P均＜0.05）;内膜PCNA阳性表达率分别为（45.32±7.21）、（36.54±6.42）和（28.57±6.31）％,各组间差异均有统计学意义（P均＜0.05）;中膜Objective To investigate the role of NF-κB/survivin signal pathway in the intima hyperplasia of rat carotid balloon injury restenosis model.Methods NF-κB siRNA lentivirus vector（titer was 1 × 108 TU/ml）was established.Carotid balloon injury restenosis model was made in 33 SD rats.The rats were divided into 4 groups according to different processing methods,including negative control （NC） group （n =11）,NF-κB siRNA group（n =11）,NF-κB siRNA ＋ YM155 （survivin inhibitor） （n =11）,the uninjured carotid artery served as the normal control group（n =1 1）.After 7 days,the carotid sample（n =5 each group）were harvested to detect the NF-κB and survivin mRNA expression by RT-PCR.The carotid sample were harvested on 28 days （n =6 each group） for HE staining and measuring intima hyperplasia.Immunohistochemical method was also used to detect the expression of intima proliferation cell nuclear antigen （PCNA） and media α-SM-actin.Results （1） After 7 days,NF-κB and survivin mRNA expression was significant higher in NC group than in normal control group （P ＜ 0.05）,the NF-κB mRNA expression was significantly lower in NF-κB siRNA group than in NC group （P ＜ 0.05） and similar between NF-κB siRNA group and NF-κB siRNA ＋ YM155 group.The survivin mRNA expression was significantly lower in NF-κB siRNA group compared to NC group （P ＜ 0.05） and significantly higher in NF-κB siRNA group than in NF-κB siRNA ＋ YM155 group （P ＜0.05）.（2） After 28 days,intima hyperplasia was observed in NC （0.13 ±0.01）,NF-κB siRNA （0.11 ±0.01） and NF-κB siRNA ＋YM155 group（0.09 ±0.01）mm2（P ＜ 0.05）.Media area was similar among NC group,NF-κB siRNA group and NF-κB siRNA ＋ YM155 group （P ＞ 0.05）.L/M ratio was gradually reduced among NC group（1.55 ± 0.07）,NF-κB siRNA group（0.92 ± 0.08）,NF-κB siRNA ＋ YM155 group（0.76 ±0.06,all P ＜0.05）.Similar results were found in the residual restenosis rate：NC group （58.71 ± 0.02） �

关 键 词：NF-κB 生存素 血管内膜 增生 

分 类 号：R543.4[医药卫生—心血管疾病] R-332[医药卫生—内科学]