【摘要】 目的:观察血管紧张素Ⅱ受体Ⅰ阻滞剂Valsartan对家兔颈动脉球囊损伤模型动脉中膜血管平滑肌细胞增殖、迁移的抑制作用。方法:健康家兔制作颈动脉球囊损伤模型,随机分为对照组(n=10)和Valsartan治疗组(n=10),治疗组术后予Valsartan喂食,10mg/(kg·d),共10天,对照组正常喂食。各组动物术前和术后3天、1、2、4、8周留取静脉血,放免法检测内皮素(ET-I);术后4、8周每组随即处死动物5只,HE染色、原位标记凋亡细胞(TUNEL)和增殖细胞核抗原(PCNA)免疫组化染色,应用光学显微镜和计算机图像分析系统对切片进行图像分析。结果:术后3天、1、2、4、8周治疗组血浆ET-1水平低于对照组(P<0.01);术后4周和8周治疗组血管壁平滑肌细胞凋亡率高于对照组,PCNA阳性率低于对照组(P<0.05);动脉内膜、中膜厚度和面积小于对照组(P<0.01);残余管腔面积大于对照组(P<0.01)。结论:血管紧张素Ⅱ受体Ⅰ阻滞剂Valsartan可以抑制内膜受损动脉中膜平滑肌细胞增殖和向内膜迁移,并促进其凋亡,预防受损动脉内膜过度增生,管腔狭窄。更多还原

【Abstract】 Objective: To investigate the effects of Angiotensin type 1 receptors antagonist (Valsartan) on the proliferation and migration of vascular smooth muscle cells and neointimal thickening in rabbit carotid injury model. Methods: Twenty rabbits undergoing ballon-induced injuries in right common carotids were randomly divided into control group (n = 10)and Valsartan-treated group (n = 10).Rabbits in the late group were administrated with Valsartan 10 mg/(kg·d) plus normal food and water for 10 days. Changes of the levels of plasma endothelin-1(ET-1)were measured by radioimmunoassay before operation and 3 days, 1, 2, 4, 8 weeks after operation respectively. Four weeks and 8 weeks after operation, 5 rabbits of each group were killed and the segments of ballon- injuried carotids were harvested for pathomorphological examination. The vessels were processed to examine VSMCs proliferation by hematoxylin-eosin staining, proliferation cell nuclear antigen (PCNA)immunohistochemistry staining and apoptotic body staining by terminal deocynucleotidy1 transferase mediated dUPT nick-end labeling (TUNEL). Results: The plasma levels of ET-1 increased after injury. Valsartan lowed them significantly (P < 0.01).Compared with the control group, VSMCs proliferation in medial was significantly inhibited and VSMCs apoptoese was significantly increased in Valsartan-treated group (P < 0.01).Neointimal thickening was observed in all ballon-injuied vessels. Valsartan significantly reduced the neointimal thickening and increased the lumen area(P < 0.01). Conclusion: Angiotensin type 1 receptors antagonist has remarkable inhibiting effects on VSMCs proliferation and migration, resulting in attenuating neointimal thickening in rabbit carotid injury model.更多还原