[Role of NF-κB/survivin signal pathway on intima hyperplasia of rat carotid balloon injury restenosis model].
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 = 11). 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). I/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).


CONCLUSIONS
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.
Department of Cardiology, Jingmen First People's Hospital, Jingmen 448000, China.
Wei
W
Cheng
Department of Cardiology, Jingmen First People's Hospital, Jingmen 448000, China.
Changjin
C
Deng
Department of Cardiology, Jingmen First People's Hospital, Jingmen 448000, China.
Luping
L
Jin
Department of Cardiology, Jingmen First People's Hospital, Jingmen 448000, China.
Ling
L
Shao
Department of Cardiology, Jingmen First People's Hospital, Jingmen 448000, China.
Xiaodong
X
Xu
Department of Cardiology, Jingmen First People's Hospital, Jingmen 448000, China; Email: shuchunming000@163.com.
Chunming
C
Shu
D000818:Animals; D002339:Carotid Arteries; D017536:Carotid Artery, Common; D016893:Carotid Stenosis; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004730:Endothelium, Vascular; D006965:Hyperplasia; D008869:Microtubule-Associated Proteins; D009131:Muscle, Smooth, Vascular; D032389:Myocytes, Smooth Muscle; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D000077022:Survivin; D017539:Tunica Intima
C516989:Birc5 protein, rat; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; D000077022:Survivin