Role of NF-κB/survivin signal pathway on intima hyperplasia of rat carotid balloon injury restenosis model
10.3760/cma.j.issn.0253-3758.2015.03.013
- VernacularTitle: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
- Author:
Wei CHENG
1
;
Changjin DENG
;
Luping JIN
;
Ling SHAO
;
Xiaodong XU
;
Chunming SHU
Author Information
1. 448000,荆门市第一人民医院心内科
- Keywords:
NF-κappa B;
Survivin;
Tunica intima;
Hyperplasia
- From:
Chinese Journal of Cardiology
2015;43(3):248-253
- CountryChina
- Language:Chinese
-
Abstract:
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) ％,NF-κB siRNA group (32.13 ± 0.05) ％,NF-κB siRNA + YM155 group (26.42 ± 0.03) ％ (all P ＜ 0.05) and expression of vascular smooth muscle cell PCNA:NC group(45.32 ± 7.21) ％,NF-κB siRNA group(36.54 ± 6.42) ％,NF-κB siRNA + YM155 group(28.57 ± 6.31)％ (all P ＜ 0.05).On the contrary,the IOD of α-SM-actin in media increased gradually:NC group (0.055 ± 0.006),NF-κB siRNA group (0.072 ± 0.011),NF-κB siRNA + YM155 group(0.084 ±0.008,all P ＜ 0.05).Conclusion Inhibiting NF-κB expression can significant decrease intima hyperplasia in this model,and this effect may be mediated by inhibiting survivin and reducing the proliferation of vascular smooth muscle cells.
