目的:以球囊损伤SD大鼠模型颈动脉内膜增生为基础,比较西洛他唑给药组和生理盐水对照组大鼠血管内膜增生强度和平滑肌细胞增殖能力方面的差异。方法:①实验于2004-01/12在解放军沈阳军区总医院全军心血管病研究所完成。实验选用健康雄性SD大鼠,体质量300～500g。②建立动物模型:腹腔麻醉36只大鼠后,暴露左颈总动脉及颈内、外动脉,自颈外动脉向近心端插入2FFogarty球囊导管至颈总动脉起始部,球囊充水0.10～0.15mL,慢速回拉至颈内外动脉分叉处,反复3次,完成后结扎颈外动脉。③36只SD大鼠随机分为2组,每组18只,分别为生理盐水组,西洛他唑给药组(7.5×10-7mol/L)。给药方式:灌肠给药,5mL/次,术后即刻开始,持续给药28d。④观察并比较两组大鼠损伤血管壁各成分结构变化图像定量分析结果。应用免疫组化分析大鼠动脉血管壁增殖情况,并应用反转录聚合酶链式反应分析两组损伤的动脉半胱天冬酶3在mRNA水平表达变化。结果:大鼠36只均进入结果分析。①大鼠动脉血管壁增殖情况免疫组化分析结果:西洛他唑给药组Ki67免疫组化染色阴性,细胞增殖能力下降;生理盐水组Ki67免疫组化染色阳性,细胞增殖能力旺盛。②损伤血管壁各成分结构变化图像定量分析结果:西洛他唑给药组大鼠颈动脉血管壁损伤后28d内膜增生面积明显小于生理盐水组犤(0.015±0.002),(0.197±0.004)mm2,t=299.06,P<0.01犦;管腔面积明显大于生理盐水组犤(0.193±0.008),(0.011±0.008)mm2,t=118.21,P<0.01犦。两组大鼠损伤动脉中膜增生面积差异不明显(P>0.05)。③两组损伤的动脉半胱天冬酶3在mRNA水平表达反转录聚合酶链式反应分析结果:西洛他唑给药组平滑肌细胞中半胱天冬酶3表达明显高于生理盐水对照组。结论:①通过在体大鼠颈动脉内膜增生模型建立,有效地模拟了西洛他唑抑制体内血管平滑肌细胞增殖的发生过程。②西洛他唑能够有效抑制体内血管平滑肌细胞增殖并诱导其凋亡,抑制血管损伤后新生内膜的形成,为临床防治增生性血管疾病的提供理论依据。 OBJECTIVE: To investigate the difference of intimal hyperplasia and proliferation of smooth muscle cells between cilostazol-treated and saline-treated rats on the basis of carotid intimal hyperplasia in balloon-injured SD rats. Methods: ① The experiment was performed at the PLA Institute of Cardiovascular Diseases, Shenyang Military Region General Hospital, People’s Liberation Army from January to December 2004. Experimental selection of healthy male SD rats, body weight 300 ~ 500g. (2) To establish an animal model: After intraperitoneal anesthesia of 36 rats, the left common carotid artery and the internal and external carotid arteries were exposed. 2FFogarty balloon catheter was inserted from the external carotid artery to the proximal end of the common carotid artery. The balloon was filled with water 0.10 ~ 0.15mL, slowly pulled back to the bifurcation of the internal and external carotid artery, repeated 3 times, after completion of the ligation of the external carotid artery. (3) Thirty-six SD rats were randomly divided into 2 groups (18 rats in each group), which were treated with saline and cilostazol (7.5 × 10-7mol / L) respectively. Mode of administration: enema, 5mL / time, immediately after the start of continuous administration 28d. ④ Observe and compare the results of quantitative analysis of structural changes of the blood vessel wall in two groups of rats. Immunohistochemistry was used to analyze the proliferation of arterial wall in rats. Reverse transcription polymerase chain reaction (RT-PCR) was used to analyze the changes of the expression of artered caspase 3 at mRNA level. Results: All 36 rats were involved in the result analysis. (1) Proliferation of rat arterial vessel wall Immunohistochemistry results showed that the expression of Ki67 in cilostazol group was negative and the ability of cell proliferation was decreased. Ki67 immunohistochemical staining in normal saline group was strong and cell proliferation ability was strong. (2) Quantitative analysis of structural changes of damaged blood vessel wall: The area of ​​intimal hyperplasia 28 days after carotid artery wall injury in cilostazol-treated rats was significantly lower than that in saline group (0.015 ± 0.002, 0.197 ± 0.004) mm2, t = 299.06, P <0.01 犦; lumen area was significantly larger than that of saline group (0.193 ± 0.008), (0.011 ± 0.008) mm2, t = 118.21, P <0.01 犦. There was no significant difference in the area of ​​arterial intimal hyperplasia between the two groups (P> 0.05). ③ The two groups of injured arteries caspase 3 expressed at the mRNA level by reverse transcription polymerase chain reaction analysis results: cilostazol administration group smooth muscle cells caspase 3 expression was significantly higher than the saline control group. CONCLUSION: ① The establishment of carotid intima hyperplasia model in vivo effectively simulates the process of cilostazol inhibiting the proliferation of vascular smooth muscle cells in vivo. ② cilostazol can effectively inhibit the proliferation of vascular smooth muscle cells and induce apoptosis in vivo, inhibit the formation of neointima after vascular injury, and provide a theoretical basis for clinical prevention and treatment of proliferative vascular diseases.