Effects of acute hypoxia on telomere length of rat gastric mucosa tissue and underlying mechanism / 生理学报

ABSTRACT

The present study was aimed to investigate the effect of acute hypoxia on telomere length of rat gastric mucosa tissue and possible mechanism. Forty male Wistar rats were randomly divided into control group (resided in Lanzhou, 1 500 m) and experimental group (hypoxia chamber, 5 000 m). The experimental group was further divided into 3 subgroups and exposed to hypoxia for 1, 3, 7 d (n = 10), respectively. The morphological changes of the gastric mucosa tissue were observed by HE staining. By means of real-time PCR, ELISA and chemical immunofluorescence methods, the telomere length, the mRNA and protein levels of telomerase reverse transcriptase (TERT), hypoxia-inducible factor 1α (HIF-1α) and HIF-2α, and reactive oxygen species (ROS) level in gastric mucosa tissue were measured, respectively. The results showed that, with the extension of hypoxia-exposure time, the injury in gastric mucosa cells progressively became worse, and telomere length was increased gradually, along with intracellular ROS generation. The changes of TERT and HIF-1α expressions induced by acute hypoxia were in the same trend as that of telomere length. There were positive correlations between TERT mRNA expression and telomere length and between TERT and HIF-1α expressions, but not between TERT and HIF-2α mRNA expressions. These results suggest that under acute severe hypoxia environment, ROS could damage the gastric mucosa tissue cells, meanwhile the expressions of TERT and telomerase activity may be up-regulated by HIF-1α, which can elongate the telomere length and protect gastric mucosa tissue against fatal injury.