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中华胸部外科电子杂志

中华胸部外科电子杂志 ›› 2016, Vol. 03 ›› Issue (03) : 170 -176. doi: 10.3877/cma.j.issn.2095-8773.2016.03.09

所属专题： 文献；

论著

腺病毒介导TGF-β1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
崔广晖1, 李玮浩1, 刘东雷1, 李宇航1, 梁有光1, 赵松1,†()   
  1. 1. 450052　郑州大学第一附属医院胸外科
  • 收稿日期:2016-02-05 出版日期:2016-08-28
  • 通信作者: 赵松

Effects of adenovirus-mediated TGF-β1 gene transfection combined with FTY720 administration on ischemia-reperfusion injury of rat lung allografts

Guanghui Cui1, Weihao Li1, Donglei Liu1, Yuhang Li1, Youguang Liang1, Song Zhao1,†()   

  1. 1. Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
  • Received:2016-02-05 Published:2016-08-28
  • Corresponding author: Song Zhao
  • About author:
    Correspongding auther; Zhao Song, Email:
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崔广晖, 李玮浩, 刘东雷, 李宇航, 梁有光, 赵松. 腺病毒介导TGF-β1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[J]. 中华胸部外科电子杂志, 2016, 03(03): 170-176.

Guanghui Cui, Weihao Li, Donglei Liu, Yuhang Li, Youguang Liang, Song Zhao. Effects of adenovirus-mediated TGF-β1 gene transfection combined with FTY720 administration on ischemia-reperfusion injury of rat lung allografts[J]. Chinese Journal of Thoracic Surgery(Electronic Edition), 2016, 03(03): 170-176.

目的

观察腺病毒介导TGF-β1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-β1组、FTY720组和TGF-β1＋FTY720组，每组6只。移植肺再灌注后4 h，检测各项生理指标。

结果

腺病毒介导TGF-β1转基因组荧光现象显著，并确定1×1010 PFU TGF-β1基因腺病毒载体为较优转染浓度。肺移植再灌注后4 h，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(PaO2)明显降低，二氧化碳分压(PaCO2)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-β1组、FTY720组和TGF-β1＋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，PaO2明显上升，PaCO2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-β1转基因联合FTY720能有效减轻大鼠同种异体肺移植IRI。

关键词: 转化生长因子-β1, FTY720, 肺移植, 缺血-再灌注, 大鼠
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 × 1010 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) 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-α contents were significantly lower. The effect in combined treatment group exhibited a certain more remarkable alleviating tendency.

Conclusions

Adenovirus-mediated TGF-β1 gene transfection combined with FTY20 administration could effectively ameliorate the IRI of rat lung allografts.

Key words: transforming growth factor beta1, FTY720, lung transplantation, ischemia reperfusion, rat
图1 各病毒滴度组的相对荧光值比较。与PFU浓度为0组比较，①P<0.05。
图2 各组移植肺血气分析指标比较。与假手术对照组比较，①P<0.05；与空白对照组比较，②P<0.05。
图3 各组移植肺W/D比值比较。1：假手术对照组；2：空白对照组；3：空载体对照组；4：TGF-β1组；5：FTY720组；6：TGF-β1＋FTY720组与假手术对照组比较，①P<0.05；与空白对照组和空载体对照组比较，②P<0.05。
图4 各组移植肺组织TGF-β1 mRNA的表达水平比较。1：假手术对照组；2：空白对照组；3：空载体对照组；4：TGF-β1组；5：FTY720组；6：TGF-β1＋FTY720组。与假手术对照组比较，①P<0.05
图5 各组移植肺组织HE染色(×200)。A：假手术对照组；B：空白对照组；C：空载体对照组；D：TGF-β1组；E：FTY720组；F：TGF-β1＋FTY720组
图6 各组移植肺组织MDA、SOD、MPO和TNF-α水平比较。与假手术对照组比较，①P<0.05；与空白对照组和空载体对照组比较，②P<0.05
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