经冠状动脉转染转化生长因子-β1基因对大鼠移植心脏缺血-再灌注损伤的影响  

Effects of TGF-β1 gene transfection in vitro on ischemia-reperfusion injury after heart transplantation in rats

作　　者：崔广晖[1,2] 齐宇 廖崇先[2] 

机构地区：[1]郑州大学第一附属医院胸外科,郑州450052 [2]厦门大学附属中山医院心脏中心,厦门361004

出　　处：《郑州大学学报（医学版）》2010年第1期99-103,共5页Journal of Zhengzhou University(Medical Sciences)

摘　　要：目的:探讨经冠状动脉转染重组腺病毒介导的转化生长因子-β1(TGF-β1)基因对大鼠移植心脏缺血-再灌注损伤的影响。方法:利用Cuff技术建立颈部异位心脏移植模型。转基因组供心离体灌注含5×109pfu/gm携带mTGF-β1基因腺病毒颗粒的4℃Stanford大学停跳液,空白对照组灌注4℃Stanford大学停跳液,空载体组灌注含5×109pfu/gm空白载体的4℃Stanford大学停跳液。移植术后8h切取移植心脏,电镜下观察移植物超微结构。免疫组化染色检测移植物mTGF-β1、细胞间黏附分子-1(ICAM-1)及核因子-κB(NF-κB)的表达。结果:移植后8h,与其他2组相比,转基因组心肌细胞肿胀减轻,炎性细胞浸润减少,心肌线粒体水肿明显减轻,无明显的肌丝断裂现象。空白对照组与空载体组无外源性mTGF-β1蛋白的表达,转基因组有mTGF-β1的表达。3组间相比,心肌组织ICAM-1与NF-κB的表达差异有统计学意义(F=23.8,P=0.008;F=36.7,P=0.007)。转基因组ICAM-1与NF-κB的表达较空白对照组与空载体组降低(P<0.01)。结论:经冠状动脉灌注重组腺病毒介导的TGF-β1基因能减轻移植心脏缺血-再灌注损伤,其机制可能与下调ICAM-1及NF-κB的表达有关。Aim：To investigate the effects of adenoviral mTGF-β1 gene transfection in vitro on ischemia-reperfusion injury after heart transplantation in rats.Methods：The model of heterotopic cardiac transplantation was established by Heron＇s technique with cuff vessel anastosis.In transfection group the donor hearts were perfused with 6 mL Stanford University cardioplegic solution at 4 ℃ containing 5×109 plaque-forming units/gram of adenoviral mTGF-β1 gene via coronary arteries,and 6 mL Stanford University cardioplegic solution and 6 mL Stanford University cardioplegic solution containing 5×109 plaque-forming units/gram of adenoviral vector were perfused in control group and control vector only group,respectively.All recipients were sacrificed and the donor hearts were removed at 8 h after transplantation.The ultrastructure of the graft tissue was observed under electron microscope.The expressions of mTGF-β1,ICAM-1,and NF-κB were detected using immunohistochemical staining.Results：At 8 h after transplantation,compared with control group and control vector only group,there were less cellular swelling,less inflammatory cell infiltration and less bioblast oedema of cadiocytes in transfection group.The expression of mTGF-β1 was detected in transfection group,but not detected in the two control groups.The expressions of ICAM-1 and NF-κB among the 3 groups had significant differences（F=23.8,P=0.008;F=36.7,P=0.007）.The expressions of ICAM-1 and NF-κB in transfection group were lower than those in the two control groups（P0.01）.Conclusion：It is demonstrated that adenoviral mTGF-β1 gene transfection in vitro ameliorates the myocardial ischemia-reperfusion injury in rat heart transplantation,and the down-regulation of ICAM-1 and NF-κB possibly contributes to this result.

关 键 词：转化生长因子-Β1 基因转染 缺血-再灌注 心脏移植 大鼠 

分 类 号：R654.2[医药卫生—外科学]