Heme oxygenase-1 modified mesenchymal stem cells in the treatment of ischemia-reperfusion injury in lung transplantation

Abstract

Objective To explore the protective mechanism of Heme Oxygenase-1 (HO-1) modified mesenchymal stem cells (MSC) in the treatment of lung transplantation ischemia-reperfusion injury (IRI). Methods Sixty SD rats were randomly divided into Surgical control (Ⅰ), simple MSCs (Ⅱ), empty vector-MSCs (Ⅲ), HO-1 modified MSCs (Ⅳ) were established. After establishing orthotopic left lung transplantation model in rats, group Ⅱ, Ⅲ and Ⅳ were injected with MSCs, empty vector-MSCs and HO-1-MSCs from pulmonary artery fine needles of recipient rats. Four hours later, partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2), tumor necrosis factor-alpha (TNF-α), Interleukin-10 (IL-10), wet/dry ratio (W/D), superoxide dismutase (SOD), malondialdehyde (MDA) and myeloperoxidase (MPO) were measured. Histopathological examination. Detection of HO-1-mRNA expression in transplants by reverse transcription polymerase chain reaction (RT-PCR). Multigroup mean comparison using One-way ANOVA. Results PaO2: Group Ⅰ, Ⅱ, Ⅲ and Ⅳ were (70.40±4.64), (87.53±4.01), (87.27±4.06), (96.80±647) mmHg (1 mmHg=0.133 kPa) gradually increased (F=75.578, P 0.05). PaCO2: group Ⅰ, Ⅱ, Ⅲ and Ⅳ were (32.67±3.31), (27.80±2.98), (27.60±2.41), (19.87±3.02) mmHg gradually decreased (F=48.286, P 0.05). W/D: Group Ⅰ, Ⅱ, Ⅲ and Ⅳ were (4.96±0.22), (4.04±0.28), (4.11±0.31), (3.85±0.27) gradually decreased (F=48.992, P 0.05). MDA content: In group Ⅰ, Ⅱ, Ⅲ and Ⅳ, the levels of MDA were (126.80±11.14), (114.27±16.45), (114.06±17.68), (102.40±14.21) nmol/g gradually decreased (F=6.551, P 0.05). MPO content: group Ⅰ, Ⅱ, Ⅲ and Ⅳ were (53.51±3.06), (45.07±3, 32), (44.45±3.37), (40.60±2.47) U/g decreased gradually (F=46.907, P 0.05). SOD activity: In group Ⅰ, Ⅱ, Ⅲ and Ⅳ, SOD activity increased gradually [(304.60±34.74), (329.87±19.44), (329.87±19.44), (338.73±15.77) U/g, (F=6.038, P 0.05). TNF-α: In group Ⅰ, Ⅱ, Ⅲ and Ⅳ, the levels of TNF-αwere (61.56±2.83), (48.32±4.11), (48.53±4.20), (36.77±3.79) ng/L gradually decreased (F=108.215, P 0.05). IL-10: The levels of IL-10 in group Ⅰ, Ⅱ, Ⅲ and Ⅳ were (23.43±2.37), (34.96±3.04), (35.48±3.00), (41.16±3.12) ng/L gradually increased (F=98.751, P 0.05). Under light microscopy, neutrophils infiltrated pulmonary interstitium and inflammatory exudation was seen in alveolar cavity. Inflammation in group Ⅳ was the lightest in each group. The amplification bands of HO-1 mRNA in group IV were significantly stronger than other groups. Conclusion HO-1 gene modified MSCs have synergistic anti-injury effect in the treatment of lung transplantation IRI. Key words: Heme oxygenase-1; Mesenchymal stem cells; Lung transplantation ischemia-reperfusion injury