摘要
目的探讨组织型纤溶酶原激活物基因质粒在预防动脉粥样硬化及血栓形成中的作用。方法新西兰纯种兔20只,分为基因治疗组和模型组,每组各10只,基因治疗组双侧髂动脉内膜剥脱术+转基因治疗+高胆固醇饮食喂养;模型组双侧髂动脉内膜剥脱术+高胆固醇饮食喂养。4周后处死动物,观察动脉内粥样硬化病变和血栓形成;在处死动物的同时抽血检测D-二聚体含量。结果成功建立了兔髂动脉粥样硬化模型并获得了组织型纤溶酶原激活物在血管周围肌肉组织中的有效表达。构建的组织型纤溶酶原激活物基因质粒可显著抑制兔动脉血管损伤后平滑肌细胞增殖细胞核抗原表达(13.55±8.43比27.78±12.35)和血小板源生长因子BmRNA表达(3.54±1.78比20.40±11.25),显著减少血管内膜厚度(32.75±21.50μm比165.70±71.21μm)和内膜面积(0.41±0.47mm2比2.01±1.15mm2),且显著抑制了局部血管粥样硬化病变发展并使病变血管内血栓形成明显减少。结论构建的组织型纤溶酶原激活物基因质粒可用于预防兔实验性动脉粥样硬化血栓形成。
Aim To elusidate the effect of tissue-type plasminogen activator （tPA} gene plasmid on prevention of the thrombosis after atherosclerosis. Methods Twenty New Zealand rabbits were＇divided into two groups （10 for experiment and 10 for control ） randomly. All the animals were done with endarterectomy of the iliac arteries and with hypercholesterole feeding after the operation. In experimental group, a 10 cm long gene suture immersed with construced tPA gene plasmid was sutured in the muscle around the injured arteries. All the rabbits were executed 4 weeks after the operation and the local artery pathology including atherosclerosis and thrombosis, the blood D-dimer concentration were ob- served. Results A model of rabbit iliac artery atherosclerosis was successfully constructed and the transfection of tPA gene plasmid and tPA expression in local muscle tissue arround the injured arteries was obtained effectively. The constructed tPA gene plasmid could inhibit the expressions of PCNA （ 13.55 ± 8.43 vs 27.78 ± 12.35 ） and platelet-derived growth factor （ PDGF-B ） mRNA （3.54 ± 1.78 vs 20.40 ± 11.25 ） by vascular smooth muscle cell （ VSMC ） after vascular injury remarkably and could reduce the intimat thickness （32.75 ± 21.50 μm vs 165.70±71.21μm） and area （0.41 ± 0.47 mm^2 vs 2.01 ± 1.15 mm^2） , and restrict the development of atherosclerosis and lumen thrombosis successfully.Conclusion Constructed tPA gene plasmid could be used for prevention of the thrombosis after rabbit experimental atherosclerosis.
出处
《中国动脉硬化杂志》
CAS
CSCD
2008年第11期844-848,共5页
Chinese Journal of Arteriosclerosis
基金
深圳市科技局资助项目(200104048)
