An Experimental Study Of Hypoxia Inducible Factor-1α And Its Target Genes Expressed In Spinal Injury

Hypoxia inducible factor 1α(HIF-1α) is a transcription factor which is expressed when cells are subjected to hypoxia. HIF-1αcan activate a serial of target genes, which are essential for tissue cells to tolerate and ameliorate hypoxia environment. It is known that hypoxia and ischemic damage also plays an important role in secondary spinal injury. Our purpose was to find out the expression pattern and effects of HIF-1αand its target genes in experimental injured spinal. In our study, static compression model was used to cause experimental spinal injury. Animals were randomizedly divided into several groups, which were sampled at different course (from 6h to 2w), and with a group of normal animals as control. In the first part, we studied HIF-1αexpression pattern in injured spinals at mRNA and also protein levels. Using RT-PCR and ISH, we detected that HIF-1αmRNA increased from 12h after injured, and reached expressional climax at 3d, and then HIF-1αprotein was inspected by monoclone antibody, results indicated that the accumulation of HIF-1αprotein emerged earlier than mRNA. In the second part, some factors mediated by HIF-1αwere studied in injured spinals. Through enzyme histochemistry and immunoh-istochemistry, LDH-M, ALDA, iNOS and VEGF were detected respectively, results showed that there was a delayed period before these factors expressed, they all highly expressed at 2 or 3 days after injured, and the patterns of their expression corresponded with HIF-1αprotein. As a hypoxia response, the emergence of HIF-1αin injured areas indicates that hypoxia-ischemic damage exists in spinal injury, hypoxia circumstance can induce the transcription of HIF-1αmRNA and the stability of its protein. Glycolytic enzymes, iNOS, VEGF all express highly in injured areas, and change dramatically according to HIF-1αprotein level. The facts reveal that HIF-1αactivate the transcription of the factors described above, HIF-1αand its target genes jointly constitute a self-protect system to alleviate hypoxia and ischemic damage in acute spinal injury. This mechanism can be utilized to treat acute spinal injury.