血管紧张素Ⅱ2型受体在体可调控表达对大鼠颈动脉新生内膜增生的影响  

Angiotensin Ⅱ type 2 receptor gene mediated by the tetracycline-regulatable system inhibits neointimal hyperplasia in rat carotid arteries after balloon angioplasty

作　　者：苗莉[1] 罗先润[1] 景涛[2] 张辉[1] 刘安丰[1] 娄云霄[1] 何国祥[2] 

机构地区：[1]武警河南总队医院心内科,郑州医学博士450052 [2]第三军医大学西南医院心内科,重庆400037

出　　处：《医学研究生学报》2011年第9期900-903,共4页Journal of Medical Postgraduates

基　　金：国家自然科学基金(30400180)

摘　　要：目的血管紧张素Ⅱ2型受体(angiotensinⅡtype 2 receptor,AT2R)基因转染可减轻血管损伤后新生内膜的过度增生,但如何主动调控转入体内基因的表达有着重要的临床意义。文中以四环素可调控系统下的AT2R基因转染的骨髓间充质干细胞(m esenchymal stem cell,MSC)为载体,探讨AT2R在体可调控表达及对大鼠颈动脉新生内膜的影响。方法大鼠颈动脉球囊损伤后,分别将PBS液、常规培养的大鼠MSC、四环素可调控系统下的AT2R基因转染的MSC局部灌注,后者又分为给予强力霉素(deoxycyline,Dox)及不给予强力霉素组。于术后14、28 d取材,分析新生内膜增生情况,免疫组化法及逆转录-多聚酶链反应(RT-PCR)检测AT2R在大鼠颈动脉壁中的表达变化。结果导入转染AT2R-MSC+Dox组大鼠颈动脉新生内膜面积较其他各损伤组显著降低(P<0.01),同时AT2R的表达显著增高;MSC对血管内膜增生无明显影响。结论四环素可调控AT2R基因在体可调控表达系统受到Dox的有效控制,可显著抑制动脉损伤后新生内膜的增生。Objective Transducing the angiotensin Ⅱ type 2 receptor（AT2R） gene into rat balloon injury carotid arteries can attenuate neointimal hyperplasia,but how to regulate the expression of the AT2R gene according to our need is very important in utilizing transgenic technology.The purpose of the current study is to investigate the effects of the AT2R gene medicated by the tetracycline regulatable system on neointimal hyperplasia in rat carotid arteries after balloon angioplasty.Methods After establishment of the rat model of carotid balloon injury restenosis,we locally perfused into the rat carotid arteries PBS（the control group）,mesenchymal stem cells（the MSC group） or MSC/AT2R（the MSC/AT2R group） with AT2R medicated by the tetracycline regulatable system,the latter again subdivided into a doxycycline administration（Dox） and non-doxycycline Dox administration（non-Dox） group.At 14 and 28 days after the operation,we evaluated the expression of AT2R by immunohistochemistry and RT-PCR and measured the neointima/media（I/M） area ratio was by morphometric analysis.Results In the MSC/AT2R ＋ Dox group,the expressions of AT2R mRNA and protein in the neointima were significantly up-regulated from day 14 to 28 after injury（P0.01）,and the I/M ratio significantly reduced（P0.01）.The transplanted MSC showed no obvious effect on the neointimal hyperplasia.Conclusion The expression of the AT2R gene can be regulated efficiently in vivo by local delivery of MSC with dual-stable expression of the AT2R gene,and thus inhibit neointimal hyperplasia.

关 键 词：血管紧张素Ⅱ受体 新生内膜 强力霉素 

分 类 号：R543.4[医药卫生—心血管疾病]