Beller Carsten J, Horvath Eszter, Kosse Jens, Becker Alexander, Radovits Tamás, Krempien Robert, Berger Irina, Hagl Siegfried, Szabó Csaba, Szabó Gábor
Department of Cardiac Surgery, University of Heidelberg, INF 326, 69120 Heidelberg, Germany.
Clin Res Cardiol. 2007 Jan;96(1):8-16. doi: 10.1007/s00392-006-0446-z. Epub 2006 Oct 10.
We investigated in a surgical rat model of vascular injury the potential role of the peroxynitrite - poly(ADPribose) polymerase (PARP) pathway in inflammatory response and apoptosis induction after vascular gamma irradiation.
Male Sprague-Dawley rats underwent left carotid endarterectomy with removal of intima: control (n = 10) and were irradiated with 15 Gray (n = 13) or 20 Gray (n = 10) postoperatively and compared with sham-operated rats (n = 10). Additional animals were solely irradiated with 15 Gy (n = 10) and with 20 Gy (n = 10) to distinguish between primary effects of vascular injury and secondary effects due to irradiation.
After 21 days, neointima formation was significantly suppressed after irradiation (control: 0.07 mm(2) +/- 0.04 mm(2), 15 Gy: 0.003 mm(2) +/- 0.004 mm(2), 20 Gy: 0.001 mm(2) +/- 0.0006 mm(2), P< 0.0001). However, a significant inflammation of the vessel wall with focal wall necrosis was detected (control: 0.2 +/- 0.15, 15 Gy: 0.82 +/- 1.2, 20 Gy: 1.25 +/- 0.86, P= 0.003). Immunohistochemistry showed significant staining for nitrotyrosine, poly(ADP-ribose) and nuclear translocation of apoptosis-inducing factor in the neointima of the control group. In the irradiated groups these stainings were significantly higher in the media and adventitia compared to the non-irradiated groups.
Activation of the peroxynitrite-PARP pathway was demonstrated during neointima proliferation in a rat model of surgical vascular injury. Vascular irradiation suppressed neointima formation, but induced significant activation of the peroxynitrite - PARP pathway in the outer vessel wall layers concomitant to inflammation and focal wall necrosis. This may contribute to adverse effects of vascular irradiation such as fibrosis and constrictive remodeling.
我们在血管损伤的手术大鼠模型中研究了过氧亚硝酸盐-多聚（ADP-核糖）聚合酶（PARP）途径在血管γ射线照射后炎症反应和细胞凋亡诱导中的潜在作用。
雄性Sprague-Dawley大鼠接受左颈动脉内膜切除术并去除内膜：对照组（n = 10），术后分别接受15格雷（n = 13）或20格雷（n = 10）照射，并与假手术大鼠（n = 10）进行比较。另外的动物单独接受15 Gy（n = 10）和20 Gy（n = 10）照射，以区分血管损伤的原发性效应和照射引起的继发性效应。
21天后，照射后新生内膜形成明显受到抑制（对照组：0.07 mm²±0.04 mm²，15 Gy：0.003 mm²±0.004 mm²，20 Gy：0.001 mm²±0.0006 mm²，P<0.0001）。然而，检测到血管壁有明显炎症并伴有局灶性壁坏死（对照组：0.2±0.15，15 Gy：0.82±1.2，20 Gy：1.25±0.86，P = 0.003）。免疫组织化学显示对照组新生内膜中硝基酪氨酸、多聚（ADP-核糖）和凋亡诱导因子的核转位有明显染色。在照射组中，与未照射组相比，这些染色在中膜和外膜中明显更高。
在手术性血管损伤大鼠模型的新生内膜增殖过程中证明了过氧亚硝酸盐-PARP途径的激活。血管照射抑制了新生内膜形成，但在与炎症和局灶性壁坏死相关的外血管壁层中诱导了过氧亚硝酸盐-PARP途径的明显激活。这可能导致血管照射的不良影响，如纤维化和狭窄性重塑。
