Nishie Hiroyuki, Takahashi Toru, Inoue Kazuyoshi, Shimizu Hiroko, Morimatsu Hiroshi, Toda Yuichiro, Omori Emiko, Akagi Reiko, Katayama Hiroshi, Morita Kiyoshi
Department of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama 700-8558, Japan.
Mol Med Rep. 2009 Mar-Apr;2(2):149-52. doi: 10.3892/mmr_00000075.
The intestine is a major target organ in hemorrhagic shock (HS)-induced tissue injury. Hypoxia-inducible factor (HIF)-1α is the primary transcription factor responsible for regulating cellular response to changes in oxygen tension. Since HS is an acute hypoxic insult, the present study examined changes in the gene expression of HIF-1α in various regions of the intestine, as well as the distribution of HIF-1α protein in the intestinal cells of a rat model of HS. Levels of HIF-1α mRNA were marginally detectable in the intestine of sham-operated control animals, but obviously induced following HS. Duodenal, jejunal and colonic levels of HIF-1α mRNA robustly increased and reached a maximum during the ischemic phase of HS, followed by a rapid decrease almost to control levels during the early phase of resuscitation. The induction of HIF-1α mRNA was maximal in the duodenum. In contrast to the duodenum, jejunum and colon, in the ileum the HIF-1α mRNA level did not increase after HS. Consistent with enhanced HIF-1α gene expression, HIF-1α protein was expressed in the mucosal cells of the duodenum, jejunum and colon, but not in the ileum following HS. These findings indicate that intestinal HIF-1α expression was up-regulated at both the transcriptional and protein level in a site-specific manner in this rat model of HS. Differential regulation of HIF-1α expression along the longitudinal axes of the intestine might be a determinant of the adaptive response to HS-induced intestinal damage.
肠道是失血性休克（HS）诱导的组织损伤的主要靶器官。缺氧诱导因子（HIF）-1α是负责调节细胞对氧张力变化反应的主要转录因子。由于HS是一种急性缺氧损伤，本研究检测了HS大鼠模型肠道不同区域HIF-1α基因表达的变化，以及HIF-1α蛋白在肠道细胞中的分布。在假手术对照动物的肠道中，HIF-1α mRNA水平勉强可检测到，但在HS后明显诱导升高。十二指肠、空肠和结肠的HIF-1α mRNA水平在HS缺血期显著升高并达到最大值，随后在复苏早期迅速下降至几乎接近对照水平。十二指肠中HIF-1α mRNA的诱导最为显著。与十二指肠、空肠和结肠不同，HS后回肠中的HIF-1α mRNA水平没有升高。与增强的HIF-1α基因表达一致，HS后HIF-1α蛋白在十二指肠、空肠和结肠的黏膜细胞中表达，但在回肠中不表达。这些发现表明，在该HS大鼠模型中，肠道HIF-1α表达在转录和蛋白水平均以位点特异性方式上调。沿肠道纵轴对HIF-1α表达的差异调节可能是对HS诱导的肠道损伤适应性反应的一个决定因素。
