腺病毒介导N19RhoA基因转染抑制大鼠颈动脉球囊损伤后新生内膜形成  

Adenovirus mediated N19RhoA gene transfer attenuates neointimal formation in rats after carotid artery balloon injury

作　　者：楚玉峰[1] 陈闻东[2] 蒋进皎[1] 孟玫[1] 曾娟[1] 王春亭[1] 高平进[2] 

机构地区：[1]山东大学附属省立医院内科重症监护病房,济南250021 [2]上海交通大学附属瑞金医院

出　　处：《中华心血管病杂志》2012年第7期601-606,共6页Chinese Journal of Cardiology

基　　金：山东省优秀中青年科学家科研奖励基金（BS2011YY043）

摘　　要：目的探讨小分子G蛋白RhoA在大鼠颈动脉球囊损伤后新生内膜形成中的作用和相关机制。方法将3～4月龄健康雄性SD大鼠分为5组：A组为正常对照组（10只）；B组为颈动脉球囊损伤组（10只）；C组为颈动脉球囊损伤＋Ad—CMV—eGFP＋PluronicF-127生物胶组（10只）；D组为颈动脉球囊损伤＋Ad—CMV—N19RhoA—eGFP组＋PluronicF-127生物胶（10只）；E组为颈动脉未损伤＋Ad—CMV—eGFP＋PluronicF-127生物胶组（10只）。建立颈动脉球囊损伤大鼠模型后，经血管外膜途径局部转染表达目的基因N19RhoA的重组腺病毒，分析其对损伤血管新生内膜增生及组织中细胞增殖核抗原和α平滑肌细胞肌动蛋白表达的影响。结果大鼠颈动脉球囊损伤后14d，B组RhoA蛋白表达量高于A组（P〈0．01）。免疫组织化学检查显示，血管组织中细胞增殖核抗原和α．平滑肌细胞肌动蛋白的阳性细胞率C组分别为45．2％和75．6％，D组分别为28．4％和51．9％，两组间差异均有统计学意义（P均〈0．01）。D组血管新生内膜面积小于C组[（0．14±0．08）mm。比（0．23±0．10）mm^2，P〈0．01]，管腔面积大于c组[（0．47±0．11）mm^2比（0．31±0．06）mm^2，P〈0．01]。结论基因转染N19RhoA可抑制颈动脉球囊损伤后局部新生内膜形成，该作用可能与RhoA参与血管外膜成纤维细胞的增殖、表型转化以及迁移有关。Objective To investigate the role of small G-protein RhoA in neointimal formation following rat carotid artery balloon injury and related mechanisms. Methods Male 3-4-month-old Sprague- Dawley rats were used in the present study （10 rats per group）. Group A： control; Group B： carotid artery balloon injury; Group C： injury ＋ Ad-CMV-eGFP ＋ Pluronic F-127; Group D： injury ＋ Ad-CMV- N19RhoA -eGFP ＋ Pluronic F-127; Group E： non injury ＋ Ad-CMV-eGFP ＋ Pluronic F-127. Perivascular gene transfer of an adenovirus co-expressing N19RhoA was performed to rat carotid artery following balloon injury and the effect on neointimal formation and the expressions of PCNA and ct-SM-actin examined. Rats were killed after 14 days. Results The protein expression of RhoA in group B was significantly higher than in group A （ P = 0. 001 ） , and the positive cells rate of PCNA and ct-SM-actin which were assessed by immunohistochemistry in group C （45.2% and 75.6% ） was significantly higher than in group D （28. 4% and 51.9% , all P 〈 0. 01 ）. The area of neointima was significantly smaller [ （0. 14 ±0. 08 ）mm2 vs. （0. 23 ±0. 10） mmz, P 〈0.01 ], the luminal area was significantly larger [ （0. 47 ±0. 11 ） mm2 vs. （0. 51 ±0. 06） mm2 , P 〈 0. 01 1 in group D than in group C. Conclusion Gene transfer of N19RhoA attenuates neointimal formation after balloon injury in rat carotid arteries possibly related to the modulating capacities of small G-protein RhoA on the proliferation, phenotypic differentiation and migration of vascular adventitial fibroblasts.

关 键 词：GTP结合蛋白质类 血管内膜 转染 

分 类 号：R54[医药卫生—心血管疾病]