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

doi:10.3877/cma.j.issn.2095-8773.2016.03.09

Abstract

Abstract:

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, PaO₂levels 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

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.

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References 18

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