Hypoxia can induce the expression of a variety of molecules, among which hypoxia-inducible factor-1 (HIF-1) acts as a key transcription factor. HIF-1 is a heterodimer composed of two subunits, HIF-1α and HIF-1β. HIF-1β is stably expressed in cells, and oxygen molecules mainly regulate HIF-1 activity through HIF-1α. Under normoxic conditions, most HIF-1α protein is degraded; while under hypoxic conditions, its expression is upregulated and degradation is inhibited, resulting in a relative increase in HIF-1α protein levels. Previous studies have demonstrated that under hypoxic conditions, HIF-1 upregulates the transcription of downstream genes, including multiple pro-fibrotic molecules, to facilitate organismal adaptation to hypoxic microenvironments. Therefore, in this study, ligation of the proper hepatic artery was performed to induce hepatic hypoxia and ultimately establish liver fibrosis.

SD rats (male, 8 weeks old)
Modeling method: In the model group, the proper hepatic artery was isolated and ligated with silk thread. In the sham operation group, the proper hepatic artery was only isolated without ligation.
Evaluation indexes: body weight change measurement, gross observation, HE staining, Sirius red staining

Body weight change measurement and gross observation of liver tissue

Hepatic tissue HE staining

Hepatic tissue Sirius red staining