腺病毒介导的线粒体融合素基因-2诱导大鼠颈动脉球囊损伤后血管平滑肌细胞凋亡  

Adenovirus-mediated Mfn2 gene induces the apoptosis of vascular smooth muscle cells after balloon injury of rat carotid artery

作　　者：廖华[1] 曹文静[1] 陈莉莉[1] 陈光慧[1] 郭小梅[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院心内科,武汉430030

出　　处：《中华急诊医学杂志》2006年第6期506-509,共4页Chinese Journal of Emergency Medicine

基　　金：国家重点基础研究发展规划项目(973)基金(G2000056906);国家自然科学基金资助项目(30570730)

摘　　要：目的研究腺病毒介导的线粒体融合素基因2(mitofusin2gene,Mfn2)对大鼠颈动脉球囊损伤后血管平滑肌细胞(vascularsmoothmusclecells,VSMCs)凋亡的影响。方法建立大鼠颈动脉球囊损伤模型,用携带大鼠Mfn2基因(rMfn2)的重组腺病毒Adv rMfn2GFP和含有绿色荧光蛋白基因的对照腺病毒Adv GFP分别感染球囊损伤动脉段,以磷酸缓冲液(PBS)作为未感染对照组,假手术组作为正常对照组,采用免疫组织化学方法检测外源基因表达水平;末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法(TUNEL)检测凋亡细胞;Image Pro图像分析系统进行血管定量组织形态学分析。结果病毒感染后5d,免疫组织化学证实Adv rMfn2GFP组Mfn2蛋白表达水平明显;TUNEL染色显示,Adv rMfn2GFP组的VSMCs凋亡率明显高于PBS组和Adv GFP组,假手术组未见TUNEL阳性VSMCs(n=10,P<0.01);感染后21d,Adv rMfn2GFP组的血管内膜面积及内膜中膜面积比明显低于对照组(n=10,P<0.01)。结论高表达Mfn2基因可诱导大鼠颈动脉球囊损伤后血管平滑肌细胞凋亡。Objective To study the effects of adenovirus-mediated Mfn2 gene transfeefion on the apeptosis of vascular smooth muscle cells after balloon injury of rat carotid artery. Methods Rat common carotid arteries were subjected to balloon injury and simultaneously infected with either Adv-rMfn2-GFP or Adv-GFP from the periarterial sheathes of vessels. The expression of Mfn2 protein was detected by staining with the anfi-rMfn2 polyelonal antibody. TUNEL assay was used to confirm the apeptosis cells. Neointima thickening was assessed using the intima to media area ratio （I/M） measured with a computer-based Image-Pre morphometric system. Results Five days after surgery, the rMfn2 protein level was significantly increased in arteries infected with Adv-rMfn2-GFP compared with those from other groups. The percentage of TUNEL-positive VSMCs in Adv-rMfn2-GFP group （19.8 ± 2.1 ）% was markedly augmented compared with those in Adv-GFP group （9.4 ± 1.7）% or uninfected group （7.8 ± 1.5）%, while there was no detectable TUNEL-pesitive cells in the sham group （ n = 10, P 〈 0.01）. The area of intima and intima to media area ratio （I/M） on day 21 after balloon angioplasty were markedly attenuated in Adv-rMfn2-GFP group （ n = 10, P 〈 0.01）. Conclusion Overexpression of Mfn2 gene may induce the apeptosis of vascular smooth muscle cells after balloon injury of rat carotid artery.

关 键 词：线粒体融合素基因-2 血管平滑肌细胞 凋亡 腺病毒科 基因治疗 

分 类 号：R543[医药卫生—心血管疾病]