干扰素-γ抑制兔髂动脉球囊损伤后PCNA表达及内膜增生的实验研究

Study of inhibitory effects of IFN-γ on expression of PCNA and proliferation of neointima in rabbit balloon-injured iliac artery

目的 通过对干扰素 -γ抑制兔髂动脉球囊损伤后增殖细胞核抗原 (PCNA)表达及内膜增生的实验研究 ,为临床应用干扰素 -γ(IFN -γ)防治血管损伤后再狭窄提供理论依据。方法 建立兔髂动脉球囊损伤模型 ,将 5 5只新西兰纯种兔分为正常组、对照组 (球囊损伤 )、干扰素组 (球囊损伤 +IFN -γ干预 ) 3组 ,应用Westernblot法及病理法 ,动态观察了体内给予重组IFN -γ对血管壁平滑肌细胞 (VSMC)PCNA表达及血管损伤后内膜 /中膜面积比的影响。结果 IFN -γ治疗组在术后第 2天起各时间点对PCNA表达均有明显的抑制作用 (P <0 0 5 ) ,与对照组相比 ,IFN -γ治疗组在术后第 1、2、3天及第 1、2、4周使PCNA表达量分别减少 15 2 %、5 3 6 %、2 8 6 %、33 1%、2 8 7%、2 3 7%。兔髂动脉球囊损伤后第 1、2、3天 ,各组均未见到新生内膜 ;损伤后 1周 ,IFN -γ组未见新生内膜 ,抑制率为 10 0 % ;损伤后 2周及 4周 ,IFN -γ组内 /中膜相对面积显著小于对照组 (P <0 0 5 ) ,与对照组相比 ,抑制率分别为 16 8%和 2 0 9%。结论 IFN -γ通过抑制VSMC增殖并抑制新生内膜形成 ,使其临床应用于防治血管损伤后再狭窄成为可能。

Objective This study was to observe the inhibitory effects of interferon-gamma(IFN-γ) on the expression of proliferation cell nuclear antigen(PCNA) and proliferation of neointima in rabbit balloon-injured iliac artery model,and provide a theoretical proof for IFN-γ to prevent restenosis. Methods To make rabbit balloon-injured iliac artery model, and to divide rabbits into three groups: normal group, control group (balloon-injured) and IFN-γ group (balloon injured and IFN-γ prevention). Western blot and pathologic methods were used to study the effects of IFN-γ on the expression of PCNA in vascular smooth muscle cells and the change of area ratio of neointima to media. Results From the second day after operation, the expression of PCNA was inhibited obviously at any point of time in the IFN-γ group (P<0.05). Compared with control group, the expression of PCNA decreased 15.2%,53.6%,28.6%,33.1%,28.7%,23.7% on the first day,second day,third day,the first week,second week,the third week in the IFN-γ group. On the first、second、 third day after operation, there were no neointima in any group. One week later, there were no neointima in IFN-γ group, and the inhibition was absolute.Two weeks and four weeks later, the neointima-media ratio of IFN-γ group was smaller than that of control group, and the inhibition ratio was 16.8% and 20.9%. Conclusion IFN-γ could inhibit proliferation of vascular smooth muscle cells and the formation of neointima, which made the prevention of vascular restenosis after injury possible.