Abstract
Study design:
Animal model of compressive spinal cord injury (SCI), reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization (ISH), immunohistochemistry (IHC) and enzymehistochemistry (EHC) were used to test the hypothesis that hypoxia-inducible factor-1α (HIF-1α) and the target genes activated by HIF-1α are involved in cell hypoxia tolerance and tissue vascularity to help injured tissue to go through the stress disease.
Objective:
To determine whether HIF-1α and its target genes associated with hypoxia tolerance and neovascularization take part in the pathophysiological procedure of SCI in rats.
Setting:
Yunnan University, China.
Methods:
Random-bred adult male Sprague–Dawley (SD) rats weighing 250±50 g were prepared for compressive SCI models. After receiving compressive injury at T10, rats were sacrificed at different times from 6 h to 1 week after injury. The injured cords were removed, and HIF-1α and its target genes were assayed by RT-PCR, ISH, IHC and EHC. The data were statistically analyzed.
Results:
An increase in HIF-1α mRNA expression was observed 12 h postinjury, reached a maximum at 3 days, and reduced gradually thereafter. HIF-1α protein expressed earlier than HIF-1α mRNA. Additionally, two glycolytic enzymes and vascular endothelial growth factor (VEGF), which are regulated by HIF-1α, also increased after an interval postinjury, and their expression patterns shared a same trend with that of HIF-1α protein.
Conclusion:
The findings suggested that the most important hypoxic regulatory factor HIF-1α was upregulated in involved cells by activating the transcription and increasing protein stability, and subsequently activated the expression of HIF-1α target genes, including glycolytic enzymes and VEGF in SCI. Combined with the pathologic observation, it suggested that overexpression of HIF-1α and its target genes might take part in hypoxia tolerance and vascularity of the injured spinal cord.
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Acknowledgements
This research was supported by the Department of Science and Technology of Yunnan Province (Grant No. 2003C0010Q) and Yunnan University (Grant No. 2002Q006SM, 2001KF-13).
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Xiaowei, H., Ninghui, Z., Wei, X. et al. The experimental study of hypoxia-inducible factor-1α and its target genes in spinal cord injury. Spinal Cord 44, 35–43 (2006). https://doi.org/10.1038/sj.sc.3101813
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DOI: https://doi.org/10.1038/sj.sc.3101813
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