反义细胞外信号调节激酶对移植物血管的保护作用  

The protective role of antisense ERK1/2 gene therapy upon aorta allografts

作　　者：董冲[1,2] 陈知水[1,2] 宫念樵[1,2] 陈曦林[1,2] 郭晖[1,2] 

机构地区：[1]华中科技大学同济医学院附属同济医院器官移植研究院 [2]器官移植教育部/卫生部重点实验室,武汉430030

出　　处：《中华器官移植杂志》2006年第2期99-101,共3页Chinese Journal of Organ Transplantation

基　　金：国家自然科学基金资助项目(30300324)

摘　　要：目的探讨反义细胞外信号调节激酶(ERK1/2)基因治疗对移植物血管的保护作用及可能的保护机制。方法建立BN至Lewis大鼠的腹主动脉移植模型。反义ERK1/2治疗组移植前取供者动脉血管段给予经脂质体包装的反义ERK1/2基因转染;腹主动脉移植术后1个月内受者每日从尾静脉或阴茎背静脉注入经脂质体包装的反义ERK1/2寡核苷酸100μl。对照组移植未经任何处理的血管段,移植后也无特殊处理。移植术后60d取移植段主动脉进行组织病理学观察内膜和胶原纤维变化;免疫组织化学法观察移植段血管ERK1/2基因的表达和CD4+、CD8+T淋巴细胞的浸润情况;ELISA法检测血清中细胞间粘附分子(ICAM-1)的变化。结果移植术后60d,对照组的移植动脉呈慢性移植物血管病表现,血管内膜显著增厚,移植血管中ERK1/2基因高表达,CD4+、CD8+T淋巴细胞大量浸润;反义ERK1/2基因治疗组移植动脉呈血管内膜炎改变,ERK1/2基因表达不明显,内膜有少量CD4+、CD8+T淋巴细胞;对照组ICAM-1表达显著高于反义ERK1/2治疗组(P<0.05)。结论反义ERK1/2基因治疗对移植物血管具有保护作用,可以减缓慢性移植物血管病的发生,这种保护机制可能和减少ICAM-1的表达以及减少移植血管T淋巴细胞的浸润有关。Objective To investigate the protection and possible mechanisms of antisense ERK1/2 gene therapy upon aorta allografts. Methods Male Lewis （LEW, RT11） rats received male Brown Norway （BN; RT1. An） aorta allografts. In anti-ERK1/2 gene therapy group, lipid-mediated ex vivo anti-ERK1/2 gene transfer into aorta allografts before transplantation; during one month after aorta transplantation, the recipients were intravenous injected with lipid-mediated anti-ERK1/2 oligonucleotide 100μl from vena caudalis or vena dorsalis penis everyday. The rats in control group was untreated. All rats were sacrificed 60 days after the operation and the grafted aortas were harvested. Morphometric analysis was used to determine the depth of intima and collagen fiber expression in aorta allografts. Immunohistochemistry was used to detect infiltration of CD4^＋ , CD8^＋ T lymphocyte in the transplanted vessels, and ELISA to detect the change of ICAM-1 in different groups. Results The rats in control group were presented with chronic graft arteriosclerosis, marked neointima formation was observed, with distinct expression of ERK1/2 and T lymphocyte infiltration in neointima, media and adventitia, and marked expression of ICAM-1 in serum; In anti-ERK1/2 therapy group, neointima formation was halted, just few ERK1/2 expression was detected and T lymphocytes were infiltrated in the neointima, and expression of ICAM-1 was inhibited （P〈0. 05）. Conclusion Antisense ERK1/2 gene therapy can protect aorta allografts and attenuate graft arteriosclerosis, which may be correlated with decreased expression of ICAM-1, and inhibition of the infiltration of CD4^＋ and CD8^＋ T lymphocytes.

关 键 词：细胞外信号调节激酶类 移植物 外周血管病 

分 类 号：R654.3[医药卫生—外科学]