血管内一氧化氮合酶基因转染预防脑血管痉挛的实验研究

Experimental study on the prevention of cerebral vasospasm by in vivo endovascular endothelial nitric oxide synthase gene transfer

目的采用血管内基因转染的方法,将重组内皮型一氧化氮合酶(eNOS)基因转染入蛛网膜下腔出血(SAH)后迟发性脑血管痉挛大鼠脑动脉,探讨防治SAH后迟发性脑血管痉挛的新方法。方法首先构建携带eNOS基因的重组腺病毒。采用小脑延髓池二次注血法建立大鼠SAH后迟发性脑血管痉挛模型。通过颈动脉微泵持续滴注方法进行基因转染,并设置对照组。结果第7天采用免疫组化证实重组eNOS基因表达,重组eNOS主要表达于内皮层。第7天显微镜下测定血管内eNOS转染组脑动脉环平均直径较单纯SAH组增大,电镜观察血管痉挛较单纯SAH组减轻。结论通过本研究证实采用颈动脉微泵持续滴注方法可在大鼠脑动脉表达重组eNOS,重组基因主要表达于动脉内皮细胞,可达到缓解SAH后迟发性脑血管痉挛的目的。

Objective To study a new methods to prevent delayed cerebral vasospasm after subarachnoid hemorrhage, we transfect recombinant eNOS gene to SAH rat from endovascular path. Methods We established a recombinant adenovirus vector carrying endothelial nitric oxide synthase gene. We established delayed cerebral vasospasm rat model using double-hemorrhage model. Recombinant adenovirus was injected into carotid arterial to transfect the rat. Results ]mmunohistochemistry detected recombinant eNOS mainly in endothelium of middle cerebral artery isolated from carotid-AdeNOS-transduced rats, Analysis of day 7 versus day 0 middle cerebral artery diameter for each group revealed significant spasm reduce in AdeNOS-transduced SAH rats. Conclusions Our results suggest that expression of recombinant eNOS in the endothelium of cerebral arteries of carotid-AdeNOS-transduced rats may contribute toward relieving delayed cerebral vasospasm after SAH.