氟伐他汀对兔髂动脉内皮剥脱后增生内膜的影响及其作用机制的探讨

Serial Experimental Research of Fluvastatin on Cell Proliferation and Apoptosis in Rabbit Iliac Artery after Endothelial Denudation

为探讨氟伐他汀对内膜增厚的影响及其与细胞增殖、细胞凋亡的关系 ,将雄性新西兰白兔 5 6只随机平分为用药组和非用药组 ,用高胆固醇饮食和球囊导管剥脱内皮造成动脉粥样内皮损伤 ,分别在内皮损伤后 1、2、4和8w处死动物并取髂动脉 ,用常规HE染色、免疫组织化学染色、原位细胞凋亡检测和计算机图像分析方法 ,观察氟伐他汀对动脉新生内膜厚度和内膜 中膜厚度比、平滑肌细胞增殖和细胞凋亡的影响。结果发现 ,用药组的新生内膜厚度和内膜 中膜厚度比明显薄于非用药组 (P <0 .0 1) ,PCNA阳性细胞率及Actin含量均明显少于非用药组 (P<0 .0 5 ) ,细胞凋亡率随用药时间延长而逐渐增高 ,且各时间点均高于非用药组 (P <0 .0 5 )。以上提示 ,氟伐他汀能有效抑制血管内膜过度增生 ,可能与其抑制平滑肌细胞增殖并可促进细胞凋亡有关。

Aim The aims was to investigate the effects of Fluvastatin on intimal thickening and the relationship between vascular smooth muscle cells(VSMCs) proliferation, apoptosis and intimal thickening. Methods 56 Rabbits were randomized into two groups: treatment group,non-treatment group. The atherosclerotic lesions were established with high cholesterol diets and iliac artery endothelial denudation. The animals were killed and iliac arteries were removed at 1,2,4,8 w respectively. With HE staining, immunohistochemical staining and in situ cell death detection,we observed the effects of fluvastatin on the thickness of intima and intima/media, and the proliferation of VSMCs and cell apoptosis in neointima and media. Results The thickness of neointima and I/M were thinner in treatment group than in non-treatment group. Percentages of PCNA-postive cells and the content of actin in the intima of treatment group was lower than that of non-treatment group. Percentages of apoptosis in treatment group increased with the time and was higher than that of non-treatment group (P<0.05). Conclusion Fluvastatin inhibit excessive thickening of vascular intima effectively,which may partly be related to its inhibiting the proliferation of VSMCs and promoting the apoptosis of cells.