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目的:研究自膨式雷帕霉素洗脱支架防治猪颈动脉血管成形术后近期再狭窄的有效性安全性,及其作用机制。方法:国产小型猪6只,分别行双侧颈总动脉球囊扩张损伤后,随机分为对照组(裸支架组)和实验组(雷帕霉素洗脱支架组),各置入6枚。术后4周重复动脉造影后处死动物。取出支架段血管,测算支架处血管管腔面积、新生内膜厚度与面积及管腔狭窄百分比以评价内膜增生程度。应用TUNEL法检测新生内膜细胞凋亡指数(apoptotic index,AI),免疫组化检测血管平滑肌细胞中增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)、Bcl-2、Bax表达水平。结果:雷帕霉素洗脱支架组支架内管腔面积大于裸支架组(P<0.05);新生内膜面积小于裸支架组(P<0.05);新生内膜厚度小于裸支架组(P<0.05);细胞凋亡多于裸支架组(P<0.05);PCNA阳性细胞及Bcl-2表达低于裸支架组(P<0.05);Bax表达高于裸支架组(P<0.05)。结论:雷帕霉素洗脱支架能抑制新生内膜形成,在支架植入后4周能预防猪颈动脉血管成形术后近期再狭窄的形成。可能通过上调Bax,下调Bcl-2的表达,从而抑制血管平滑肌细胞增殖发挥作用。
Objective: To study the safety and efficacy of self-expanding rapamycin-eluting stent in the prevention and treatment of recent restenosis after porcine carotid angioplasty and its mechanism. Methods: Six domestic miniature pigs were randomly divided into control group (bare stent group) and experimental group (rapamycin - eluting stent group) with 6 cases of bilateral common carotid artery balloon dilatation injury . Four weeks after the operation, animals were sacrificed after repeated arteriography. The stent segment blood vessel was removed, the lumen area, the neointimal thickness and area, and the stenosis percentage of the stent were measured to evaluate the degree of intimal hyperplasia. The apoptotic index (AI) was detected by TUNEL method and the expression of proliferating cell nuclear antigen (PCNA), Bcl-2 and Bax in vascular smooth muscle cells were detected by immunohistochemistry. Results: The area of lumen in the rapamycin-eluting stent group was larger than that of the bare stent group (P <0.05), the neointimal area was smaller than that of the bare stent group (P <0.05), and the neointimal thickness was smaller than that of the bare stent group 0.05). The apoptosis of cells was higher than that of the bare scaffolds (P <0.05). The expressions of PCNA positive cells and Bcl-2 were significantly lower than those of the bare scaffolds (P <0.05). Conclusion: Rapamycin-eluting stent can inhibit the formation of neointima. Four weeks after stent implantation, it is possible to prevent the formation of short-term restenosis after porcine carotid artery angioplasty. Probably by up-regulating Bax, down-regulating the expression of Bcl-2, thereby inhibiting the proliferation of vascular smooth muscle cells to play a role.