Protective effect of Berberine pretreatment in hepatic ischemia/reperfusion injury of rat.

Background: Berberine (BBR) has been demonstrated to protect against hepatic ischemia/reperfusion (I/R) injury. However, the exact mechanism is largely unknown. In the present study, we examined the role of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and mammalian target of rapamycin (mTOR) in the protective effect of BBR on hepatic I/R-mediated apoptosis in rats.

Methods: Adult male Sprague-Dawley rats were assigned randomly to groups of sham, ischemia/reperfusion (I/R), I/R+DMSO (vehicle) and I/R+BBR (100 mg/kg/d, 2 weeks). The hepatic cold ischemia model was established by perfusing the liver with heparinized cold saline through the portal vein for 20 minutes. The liver function and oxidative stress level were measured by biochemical and histopathologic examinations. The apoptotic rate was determined by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay. The expression of Bcl-2, Bax, caspase-3, and the phosphorylation of Akt and mTOR were assayed by Western blot analysis and immunohistochemistry.

Results: Compared with the I/R group, BBR dramatically attenuated the histopathologic damage, restored the liver function, and decreased the oxidative stress level. Simultaneously, BBR significantly ameliorated apoptosis by decreasing the apoptotic rate, increasing the Bcl-2/Bax ratio and inhibiting cleaved caspase-3 expression in rats subjected to hepatic I/R. The expression of p-Akt were effectively upregulated with the inhibited expression of p-mTOR.

Conclusion: Our study reveals that BBR preconditioning protects against hepatic I/R partly by reducing apoptosis, which is possibly involved with the modulation of the PI3K/Akt/mTOR signaling pathway.