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人组织因子途径抑制物基因在兔颈动脉损伤血栓形成中的作用

Effect of adenovirus-mediated local tissue factor pathway inhibitor gene transfer on thrombosis formation in rabbit carotid artery injuries
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摘要 目的观察人组织网子途径抑制物(tissue factor pathway inhibitor,TFPI)基因在兔颈动脉损伤血栓形成的作用。方法大耳白兔40只,体质量2.5~3.0kg。将白兔按体质量随机分为4组:腺病毒介导的TFPI基因(Ad—TFPI)转染组、腺病毒介导的LacZ基因(Ad—LacZ)转染组、磷酸盐缓冲液(PBS)组和对照组,每组10只。对照组不进行任何处理,另3组用PTCA球囊导管对白兔右侧颈动脉进行损伤,损伤处分别用Dispatch转基因导管按组别局部注射转染Ad—TFPI、Ad—LacZ液和PBS各0.2ml。转染10d后,采用相同方法对白兔颈动脉损伤处进行二次损伤,对照组进行第1次损伤,损伤后立即恢复血流。30min后处死白兔.分别取出损伤侧和对侧颈总动脉,沿长轴剪开、展平,2%戊二醛固定,扫描电镜下观察4组白兔损伤处动脉管壁血小板聚集及纤维素(血栓)形成情况。结果扫描电镜下,正常未经任何损伤的颈动脉管腔内可见血管内皮细胞结构完整,排列整齐;对照组在球囊损伤后血管内皮不完整,有部分血小板聚集,血管壁上无纤维素生成:Ad—TFPI组在二次损伤后血小板聚集增加,但血管壁上未见纤维素形成;Ad—LacZ组和PBS组可见血管壁上有大量的纤维素形成和红细胞堆积。血管壁血栓形成阳性率组间比较差异有统计学意义(χ^2=14.95,P〈0.01);其中Ad—TFPI组(20%)低于Ad—LacZ组(80%,χ^2=7.20,P〈0.01)和PBS组(70%,χ^2=5.05,P〈0.05),高于对照组(10%,χ^2=0.39,P〉0.05);Ad—LacZ组(80%)高于对照组(10%,χ^2=9.90,P〈0.01),也高于PBS组(70%,χ^2=0.27,P〉0.05);PBS组(70%,)高于对照组(10%,χ^2=7.50,P〈0.01)。结论二次球囊损伤法可造成大量血栓形成;腺病毒表达载体TFPI可以抑制动脉损伤后纤维素沉积。 Objective To observe the effects of tissue factor pathway inhibitor(TFPI) on thrombosis follnation in rabbit carotid arteries after ballon injury. Methods Fouty rabhits with the weight 2.5 - 3.0 kg were respectively divided into 4 groups, Ad-TFPI, Ad-LacZ, PBS and normal control groups. The normal control group was not given any treatment and other 3 groups were given 0.2 ml Ad-TFPI, Ad-LacZ or PBS reproduced by the Dispatch catheter respectively after the PTCA balloon iniury on the right carotid arteries. Ten days after gene transfer the repeated balloon injury was performed in the 3 groups, and the first balloon injury was performed in the normal control group by the same method. The carotid blood flow was recovered immediately after the injury. Thirty minutes later all the animals were sacrificed. The injured carotid arteries and one part of contralateral normal artery were cut down, scissored along the long axis, flattened and fixed in the 2% glutaral. The platelet aggregation and thrombosis formation on the luminal surfaces was observed under electron microscope. Results The electron microscope results showed that the vascular endothelial cell structure was integrated and lined up in order in the nomal artery which had no any injury. After the balloon injury in the normal control group, the structure of the endothelial cell was disintegrated, and there was some platelet aggregation but no fibrosis formation. A large amount of platelet aggregated but no fibrosis formed in Ad-TFPI group after the repeated balloon injury. A large amount of fibrosis formed and red cells piled up in the Ad-LacZ and PBS group. The positive rate of thrombosis formation among groups had siginificant differences(χ^2 =14.95, P 〈 0.01 ). The positive rate in Ad-TFPI group (20%)was lower than that in Ad-LacZ group(80%,χ^2= 7.20, P〈 0.01) and PBS group(70%, χ^2= 5.05, P〈 0.05), but was higher than that in the normal control group( 10%,χ^2= 0.39, P 〉 0.05). The positive rate in Ad-LacZ group(80%) wa
出处 《中国地方病学杂志》 CAS CSCD 北大核心 2009年第5期509-513,共5页 Chinese Jouranl of Endemiology
基金 国家自然科学基金(30700765) 黑龙江省青年科学技术专项基金(QC05C29)
关键词 组织因子途径抑制物 基因转染 颈动脉损伤 血栓形成 显微镜检查 电子 扫描 Tissue factor pathway inhibitor Gene therapy Carotid artery injuries Thrombosis formation Microscopy, electron, scanning
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参考文献13

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