Effects Of Oa Pretreatment On The Pi3k-akt-gsk-3β Signaling Pathway During Hiri In Rats

Backgrounds:Hepatic ischemic reperfusion injury(HIRI) is the common problem during liver surgery, shock, trauma and organization transplantation, which is also the inevitable period during the process of liver transplant. Searching the ways and measurements of protecting liver, preventing or alleviating HIRI has become the hotspots issues, apoptosis plays an important role in HIRI. Oleanolic Acid (Oleanlic Acid, OA) is a kind of pentacyclic triterpene compounds, exist widely in China plant such as clove, containing, wood, steamed bravery, selfheal, etc in plants. OA has a variety of biological activity. Du reported that OA can reduce heart ischemia-reperfusion injury; another one showed that OA can reduce cerebral ischemia-reperfusion injury. Our previous works suggested that the pretreatment of OA induced the rat's hepatic glycogen increases and alleviates the HIRI, but the mechanism is unclear.Objective:This study is to explore the effects of OA pretreatment on PI3K-AKT-GSK-3βsignaling pathway during HIRI in rats.Methods:128 Male Sprague-Dawley(SD) rats were randomly allocated into sham(SH) group, ischemic-reperfusion(IR) group,0.5%sodium carboxymethycellulose(CMC-Na,CM) group,OA+0.5% CMC-Na (OA) group. All rats were got pretreatment through intragastric administration route one time a day for seven day. Rates in OA group were taken with OA(100mg/kg)+0.5% CMC-Na, SH group,IR group with the water as same volume as OA group, CM group with 0.5% CMC-Na as same volume as OA group. On the eighth day, all rats expect SH group were suffered from segmental (70%) hepatic ischemia for 60 min and followed by different periods of reperfusion. The hepatic tissues were taken on the 8th day at preoperation, at the point of Oh,3h, and 6h after reperfusion. The protein expression of hepatic p-PI3K(p85),p-AKT(ser473),AKT,p-GSK-3β(ser9),GSK-3βwere evaluated by western blotting.Results:The protein expression of p-GSK-3β(ser9) in the OA group was increased remarkably than those in other three groups at preoperation and Oh after reperfusion (P<0.05), while there were no differences among SH, IR and CM groups (P> 0.05).The protein expression of p-PI3K(p85),p-AKT(ser473),p-GSK-3β(ser9) in the OA group were increased remarkably than those in other three groups at the point of 3h,6h after reperfusion (P<0.05), while these of SH group were more lower than other three groups(P<0.05), there were no difference between IR and CM groups (P>0.05). The total protein expressions of AKT and GSK-3βwere no differences in all groups at any time (P>0.05)Conclusion:The protein expressions of p-PI3K(p85),p-AKT(ser473),p-GSK-3β(ser9) were increased at preoperation and after reperfusion by pretreatment of OA. It is suggested that PI3K-AKT-GSK-3βsignaling pathway may be one of mechanisms for OA prevention HIRIS...