Effect of herpes simplex virus vector, d12CALP, on vasospasm in rabbit common carotid artery with atherosclerotic changes

对象：本研究旨在阐明单纯疱疹病毒（HSV）抑制血管平滑肌细胞增殖的治疗对动脉粥样硬化血管痉挛的影响。方法：我们制作了一个长期的血管痉挛模型，黑泽和草柳-高胆固醇血症兔颈总动脉周围的血管应用充满血液的硅胶片。在第0、1和2天（HSV给药组），将HSV载体d12CALP（其中钙调蛋白启动子驱动ICP 4基因，胸苷激酶启动子驱动LacZ基因）（1 × 10^9 pfu/ml）给予右侧颈总动脉。钙调蛋白是众所周知的蛋白质，它在平滑肌细胞中特异性表达，因此d12 CALP仅在分裂良好的平滑肌细胞中复制并破坏。在第7天，每只家兔灌注固定后，用X-gal染色HSV处理的颈总动脉以检测病毒复制的分布。形态测定分析，包括lum的测量 关于我们 结果：HSV感染第2天组颈动脉平滑肌细胞X-gal染色呈阳性;然而，在第0天和第1天的HSV处理组中没有蓝色染色。形态测定分析表明，在第2天，HSV-无治疗组的管腔面积显著减少，壁厚度增加。这些变化在第7天显著持续。然而，与对照组相比，在所有HSV处理组中，血管没有收缩，而是扩张。结论：在动脉粥样硬化性颈总动脉痉挛模型中，第2天即出现血管平滑肌增生。因此，我们认为HSV抑制此时的血管平滑肌细胞增殖可能为血管痉挛的治疗提供一种新的途径。少

Object: The present study was designed to clarify the effect of treatment with herpes simplex virus (HSV) inhibited vascular smooth muscle cell proliferation on vasospasm with atherosclerosis.Methods: We produced a prolonged vasospasm model of Kurosawa and Kusanagi- hypercholesterolemic rabbit common carotid artery by applying a blood-filled silicone sheet around the vessel. A HSV vector, d12CALP, in which the calponin promoter drives ICP4 gene and thymidine kinase promoter drives LacZ gene (1×10^9 pfu/ml) was administered into the right common carotid artery on Days 0, 1 and 2 (HSV-treated groups). Calponin is well-known protein which is specifically expressed in smooth muscle cells, therefore d12CALP replicates in and destroy well dividing smooth muscle cells alone. After perfusion -fixation of each rabbits on Day 7, the common carotid arteries treated with HSV were stained with X-gal to detect the distribution of virus replication. Morphometric analysis including measurements of lum … More inal area and wall thickness was also performed.Results: In HSV-treated on Day 2 group, smooth muscle cells in the carotid artery revealed positive staining with X-gal. However, there was no blue staining in HSV-treated on Days 0 and 1 groups. Morphometric analysis demonstrated a marked reduction in the luminal area as well as increase in the wall thickness on Day 2 in HSV-no treated group. These changes were significantly persistent on Day 7. In all HSV-treated groups, however, there was no constriction of the vessel and it was dilated rather, compared to the control group. Especially, in HSV-treated on Day 2 group, the degree of vasodilatation was significantly strong (P<0.01).Conclusion: In a vasospasm model of common carotid artery with atherosclerosis, vascular smooth muscle proliferation was developed on Day 2. Therefore, we considered that inhibition of the vascular smooth muscle cell proliferation at this time by HSV might provide a novel approach for the treatment of vasospasm. Less