Hepatic stellate cell activation and hepatic fibrosis induced by ischemia/reperfusion injury.

OBJECTIVE

Warm ischemia causes severe allograft damage in liver transplantation. However, the long-term effects of ischemia/reperfusion injury (IRI) on fibrosis have not been fully elucidated. In this study, we used a partial warm hepatic ischemia mouse model to monitor fibrosis in the ischemic liver.

MATERIALS AND METHODS

Male BALB/c mice were divided into ischemic and sham groups (n = 30/group). Via a midline laparotomy, an atraumatic clip was used to interrupt the arterial and the portal venous blood supply to the left liver lobe. After 90 minutes of partial hepatic ischemia, the clip was removed initiating hepatic reperfusion. Samples from normal, sham, and ischemic liver tissues were collected at intervals of 1, 5, 10, 15, 20, or 30 days after operation (n = 5 for each time point) for hematoxylin-eosin (H&E), Mallory's trichrome, and alpha-smooth muscle actin (alpha-SMA) immunohistochemical stains for fibrosis and activation of hepatic stellate cell (HSCs).

RESULTS

IRI caused significant HSC activation in the ischemic liver tissues. Mallory's trichrome stain demonstrated that IRI caused hepatic parenchymal fibrosis near portal tracts and central veins. With prolonged reperfusion time hepatic parenchymal fibrosis was aggravated, showing the same pattern of HSC activation. IRI also caused increased portal tract fibrosis in ischemic liver tissues, especially around biliary tracts.

CONCLUSIONS

Hepatic IRI caused HSC activation, increasing hepatic parenchymal and portal tract fibrosis in ischemic liver tissues.