西洛他唑调节核因子κB通路抑制炎症因子治疗兔髂动脉成形后的血管内再狭窄  

Cilostazol treats rabbit iliac artery restenosis by regulating nuclear factor kappaB pathway to inhibit inflammatory factors

作　　者：曾智桓[1] 董吁刚[2] 赵艳群[1] 黄瑞邈广东药学院附属第一医院心内科 张卫[1] 王蔚[1] 

机构地区：[1]广东药学院附属第一医院心内科,广东省广州市510080 [2]中山大学附属第一医院,广东省广州市510080

出　　处：《中国组织工程研究与临床康复》2010年第35期6573-6577,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：广东省医学科研基金立项资助课题(A2008338),课题名称:西洛他唑治疗兔髂动脉血管成形术后再狭窄的研究。立项资助1.0万元~~

摘　　要：背景:血管成形术后再狭窄发生率高,炎症反应的发生是再狭窄的始动因素,如何有效抑制炎症反应,减少平滑肌细胞迁移和增殖是降低再狭窄发生的关键。多个研究均已证实西洛他唑有确切地降低血管成形术后再狭窄作用,但其作用机制仍不明确。目的:观察西洛他唑在兔髂动脉粥样硬化球囊成形术后再狭窄中的抗炎作用,揭示其作用途径。方法:将大白兔分成6组,即空白对照组、血管狭窄组、再狭窄模型组、西洛他唑25,50及100mg/kg组。高脂饲养,除空白对照组外均制作髂动脉内皮剥脱血管狭窄模型。喂养4周后再狭窄模型组及各西洛他唑治疗组在血管狭窄部位行经皮球囊扩张成形术制作再狭窄模型。血管造影抽血测定血脂浓度及细胞因子质量浓度,以免疫组化法观察核因子κB表达,用图像工作站对血管造影结果行血管狭窄分析。结果与结论:与再狭窄模型组相比,各西洛他唑治疗组血脂浓度及细胞因子质量浓度均明显下降(P<0.05)。免疫组化显示再狭窄模型组中核因子κB表达显著高于空白对照组及各西洛他唑治疗组,治疗组随着剂量增加核因子κB表达逐渐减弱(P<0.05)。血管造影证实,各西洛他唑治疗组与再狭窄模型组相比,血管面积狭窄率及直径狭窄率明显下降(P<0.01)。结果提示,西洛他唑能够抑制兔髂动脉成形术后再狭窄,通过调节核因子κB抑制各种炎症因子可能是西洛他唑治疗再狭窄的作用途径。BACKGROUND: Restenosis after angioplasty frequently occurs. Inflammatory response is the initiating factor of restenosis. Therefore, to effectively suppress inflammation and reduce smooth muscle cell migration and proliferation is the key to reducing restenosis. Studies have demonstrated that cilostazol significantly reduces restenosis after angioplasty, but the mechanism remains unclear. OBJECTIVE: To investigate the efficacy and mechanism of the cilostazol treatment of rabbit iliac artery restenosis. METHODS: The white rabbits were randomly divided into 6 groups (blank control, vascular stenosis, vascular restenosis, cilostazol 25, 50 and 100 mg/kg groups), and fed with high fat food. Iliac artery stenosis model was established in all groups except blank control group. Percutaneous transluminal angioplasty was performed at stenosis site of vascular restenosis and cilostazol groups. Angiography was performed to determine blood lipid and cytokine mass concentration. Nuclear factor-κB expression was observed by immunohistochemistry, and vascular stenosis was analyzed using imaging work station. RESULTS AND CONCLUSION: Compared with the restenosis group, the blood lipids and cytokines concentration was significantlydecreased following cilostazol treatment (P < 0.05). Immunohistochemistry showed that the nuclear factor-κB expression in restenosis group was significantly greater than the blank control and cilostazol groups, but the expression was decreased with increasing cilostazol dose (P < 0.05). Angiography confirmed that vessel area stenosis rate and rates of diameter stenosis were significantly decreased in cilostazol group compared with the restenosis group (P < 0.01). Results showed that cilostazol can inhibit the rabbit iliac artery restenosis, possibly by regulating nuclear factor-κB and inhibiting various inflammatory factors.

关 键 词：西洛他唑 核因子ΚB 血管成形术 再狭窄 细胞因子 兔 

分 类 号：R318[医药卫生—生物医学工程]