腺病毒介导TGF-β_1转基因联合FTY720对大鼠同种异体肺移植缺血-再灌注损伤的保护作用  

Effects of adenovirus-mediated TGF-β_1 gene transfection combined with FTY720 administration on ischemia-reperfusion injury of rat lung allografts

作　　者：崔广晖[1] 李玮浩[1] 刘东雷[1] 李宇航[1] 梁有光 赵松[1] 

机构地区：[1]郑州大学第一附属医院胸外科,450052

出　　处：《中华胸部外科电子杂志》2016年第3期170-176,共7页CHINESE JOURNAL OF THORACIC SURGERY：Electronic Edition

摘　　要：目的观察腺病毒介导TGF-β_1转基因联合FTY720对大鼠同种异体肺移植缺血-再灌注损伤(IRI)的影响。方法采用改良的三袖套法吻合技术建立大鼠左肺原位移植模型。以SD大鼠为供受体,随机分为假手术对照组、空白对照组、空载体对照组、TGF-β_1组、FTY720组和TGF-β_1+FTY720组,每组6只。移植肺再灌注后4h,检测各项生理指标。结果腺病毒介导TGF-β_1转基因组荧光现象显著,并确定1×10^(10) PFU TGF-β_1基因腺病毒载体为较优转染浓度。肺移植再灌注后4h,与假手术对照组比较,空白对照组和空载体对照组出现典型的移植肺IRI症状,肺动脉血氧分压(PaO_2)明显降低,二氧化碳分压(PaCO_2)和湿/干重(W/D)比值明显升高,超氧化物歧化酶(SOD)活性明显降低,丙二醛(MDA)含量、髓过氧化物酶(MPO)活性和肿瘤坏死因子-α(TNF-α)含量明显升高。与空白对照组和空载体对照组比较,TGF-β_1组、FTY720组和TGF-β_1+FTY720组移植肺组织水肿和间质炎症等病理组织学现象明显减轻,PaO_2明显上升,PaCO_2和W/D比值明显下降,SOD活性明显增加,MDA含量、MPO活性和TNF-α含量明显降低。其中,联合处理组病理症状表现出更为明显的减轻趋势。结论腺病毒介导TGF-β_1转基因联合FTY720能有效减轻大鼠同种异体肺移植IRI。Objective To investigate the effects of adenovirus-mediated transforming growth factor beta1（TGF-β1） gene transfection combined with FTY20 administration on ischemia-reperfusion injury（IRI）of rat lung allografts.Methods By using improved“cuff-like”vessel anastomosis technique, rat orthotopic left pulmonary allograft transplantation was successfully established.SD rats were chosen as both recipients and donors,and were randomly divided into sham operation control group,blank control group,empty adenovirus control group,TGF-β1 group,FTY720 group and TGF-β1 ＋FTY720 group,with 6 rats in each group. Physiological indexes of each group were assessed 4 h after reperfusion.Results The fluorescence phenomenon accompanied with TGF-β1 adenovirus-mediated gene transfection was remarkable,and 1 × 10^10 PFU was chosen as the optimal transfection concentration. Four hours after reperfusion of lung transplantation,compared with sham operation control group,the typical pathological change of IRI was found in blank control group and empty adenovirus control group, the partial pressure of oxygen（PaO2）levels were significantly reduced,partial pressure of carbon dioxide （PaCO2） levels and weight/dry（W/D） ratios were significantly increased,superoxide dismutase（SOD） activity was significantly decreased,and malondialdehyde（MDA） contents,myeloperoxidase（MOP）＆amp;nbsp;activity and tumor necrosis factor-α（TNF-α） contents were significantly increased.Compared with blank control group and empty adenovirus control group,the histopathological manifestations such as tissue edema and interstitial inflammation were much milder in TGF-β1 group,FTY720 group and TGF-β1 ＋FTY720 group,PaO2 levels were significantly higher,PaCO2 levels and W/D ratios were significantly lower,SOD activity was significantly higher,and MDA contents,MPO activity and TNF-αcontents were significantly lower. The effect in combined treatment group exhibited a certain more remarkable alleviating tendency.Conclusions Adeno

关 键 词：转化生长因子-Β1 FTY720 肺移植 缺血-再灌注 大鼠 

分 类 号：R655.3[医药卫生—外科学]