Effect of oleanolic acid pretreatment on hepatic ischemia-reperfusion injury in rats

Abstract

Objective To investigate the effect of oleanolic acid pretreatment on hepatic ischemiareperfusion (I/R) injury in rats. Methods One hundred and twenty-eight male SD rats weighing 230-250 g were randomly divided into 4 groups (n = 32 each): sham operation group (group S), I/R group, 0.5% sodium carboxymethyl cellulose group (group CMC) and oleanolic acid preconditioning (group OA). Partial liver ischemia was produced by clamping hepatic portal vein and hepatic arteries for 60 min with atraumatic mini-clamp, followed by 12 h of reperfusion in group I/R, CMC and OA. Oleanolic acid suspension 100 mg/kg was infused intragastrically in group OA, while the equal volume of 0.5% CMC-Na (in group CMC) and drinking water (in group S and I/R) was infused intragastrically instead once a day for 7 days, and then hepatic I/R was performed at day 8. The left liver was removed and blood sample was taken from inferior vena cava at 0, 3, 6 and 12 h ofreperfusion for determination of serum alanine amino transferase (ALT) activity, superoxide dismutase (SOD)activity, malondialdehyde (MDA) and glutathione (GSH) content, and expression of phospho-phosphatidylinositol3-kinase (p-PI3K), Akt, p-Akt, Bcl-2, Bax, p-Bad and Bad in the liver, and microscopic examination. Results Serum ALT activity and MDA content in the liver were significantly increased, SOD activity and GSH content in the liver were significantly decreased, expression of p-PI3K, p-Akt, Bax, Bad and p-Bad was up-regulated, and Bcl-2 expression was down-regulated during reperfusion in group I/R, CMC and OA as compared with group S (P ＜0.05). Compared with group I/R, serum ALT activity and MDA content in the liver were significantly decreased, SOD activity and GSH content in the liver were significantly increased, expression of p-PI3K, p-Akt,Bcl-2 and p-Bad was up-regulated, and expression of Bad and Bax was down-regulated during reperfusion in group OA (P ＜ 0.05), but no significant change was found in the indexes mentioned above in group CMC (P ＞ 0.05).Serum ALT activity and MDA content in the liver were significantly lower, SOD activity and GSH content in the liver were significantly higher, expression of p-PI3K, p-Akt, Bcl-2 and p-Bad was significantly higher, and expression of Bad and Bax was significantly lower during reperfusion in group OA than in group CMC (P ＜ 0.05).The pathological changes in the liver were milder in group OA than in group I/R. Conclusion Oleanolic acid pretreatment can alleviate hepatic I/R injury by activating PI3K/Akt signaling pathway and inhibiting apoptosis. Key words: Oleanolic acid; Reperfusion injury; Liver