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| Change and significance of HIF-1α mediated by TLR4 signal pathway in the model of lung ischemia reperfusion injury rats |
| Caikai·Shareli1 XU Sicheng1 LI Chao1 DONG Xu'nan2 |
1.Department of RICU, Respiratory and Respiratory Critical Care Center, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830054, China;
2.The Fifth Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China |
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Abstract Objective To investigate the changes and significance of hypoxia inducible factor-1α (HIF-1α) mediated by Toll like receptor 4 (TLR4) signal pathway in the model of lung ischemia reperfusion injury (IRI) rats. Methods A total of 48 healthy male SD rats were selected and randomly divided into sham operation group, IRI model group, TLR4 activation group (LPS intervention) and TLR4 inhibition group (TAK-242 intervention) with 12 rats in each group. 3 weeks before model, IRI model group and sham operation group were injected with saline, TLR4 activation group was injected with lipopolysaccharide, TLR4 inhibition group was injected with TAK-242, once a week for three weeks. IRI model group, TLR4 activation group and TLR4 inhibition group were established a model of lung ischemia-reperfusion injury after last injection 30 minutes, sham operation group was treated same as the other groups except for not block the lung door. 3 hours after reperfusion injury, TLR4, HIF-1α, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA expression of lung tissue were tested by reverse transcriptase polymerase chain reaction (RT-PCR). TLR4, HIF-1α, TNF-α and IL-6 protein expression of lung tissue were tested by Western-blot. Results The lung wet weight/dry weight ratio of the IRI model group was higher than that of the sham operation group (P < 0.05), the TLR4 activation group was higher than that of the model group (P < 0.05), and the TLR4 inhibition group was lower than that of the model group (P < 0.05). The mRNA and protein expression levels of TLR4, HIF-1α, TNF-α, IL-6 in the lung tissues of IRI model group were higher than those of the sham operation group (P < 0.05), the TLR4 activation were higher than those of the model group (P < 0.05), and the TLR4 inhibition group were lower than those of the model group (P < 0.05). Conclusion The TLR4 signal pathway in the lung tissue mediates the HIF-1α expression increased significantly after lung ischemia-reperfusion injury in rats, and increases the degree of inflammatory damage to the lung tissue.
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