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目的:齐墩果酸(oleanolic acid,OA)预处理可使大鼠肝糖原增加并使肝脏缺血再灌注损伤(hepatic ischemic reperfu-sion injury,HIRI)减轻,但机制不详。本研究拟探讨OA预处理对大鼠HIRI前后的PI3K-AKT-GSK-3β信号传导通路的影响。方法:128只SD大鼠随机分为假手术组(SH组)、缺血再灌注组(IR组)、0.5%羧甲基纤维素钠组(CM组)和齐墩果酸预处理组(OA组)。OA组以100mg/kg的齐墩果酸混悬液,SH和IR组以相同容积的水,CM组以相同容积的0.5%CMC-Na分别每日灌胃1次,连续7天。第8天建立70%肝脏缺血再灌注模型,肝脏缺血60min后行再灌注。于术前(第8天)、再灌注0、3、6h取肝组织。用Western blot法测定肝组织的p-PI3K(p85)、p-AKT(ser473)、AKT、p-GSK-3β(ser9)、GSK-3β的蛋白表达量。结果:术前、再灌注0h时,OA组的p-PI3K(p85)、p-AKT(ser473)、p-GSK-3β(ser9)的蛋白表达量分别比其他3组明显增加(P<0.05);此时SH组、IR组、CM组的各蛋白表达量之间比较未见统计学差异(P>0.05)。再灌注3、6h时,OA组的p-PI3K(p85)、p-AKT(ser473)、p-GSK-3β(ser9)蛋白含量分别比其他3组显著增加(P<0.05),SH组相应时点的各蛋白含量均比其他3组的含量明显降低(P<0.05),IR组与CM组相应时点的各蛋白含量之间比较未见差异(P>0.05);各组的AKT与GSK-3β蛋白含量在各个时间点之间均未见统计学差异(P>0.05)。结论:OA预处理可使HIRI前后的p-PI3K(p85)、p-AKT(ser473)和p-GSK-3β(ser9)蛋白含量增加,激活肝脏PI3K-AKT-GSK-3β信号通路,此可能是OA减轻HIRI的机制之一。
OBJECTIVE: Oleanolic acid (OA) pretreatment can increase hepatic glycogen and reduce hepatic ischemic reperfusion-injury (HIRI) in rats, but the mechanism is unknown. This study was to investigate the effect of OA pretreatment on the PI3K-AKT-GSK-3β signaling pathway before and after HIRI in rats. Methods: 128 SD rats were randomly divided into sham operation group (SH group), ischemia reperfusion group (IR group), 0.5% sodium carboxymethyl cellulose group (CM group) and oleanolic acid pretreatment group OA group). OA group with 100mg / kg oleanolic acid suspension, SH and IR group with the same volume of water, CM group with the same volume of 0.5% CMC-Na were intragastric gavage once a day for 7 days. On the 8th day, 70% hepatic ischemia-reperfusion model was established and reperfusion was performed 60min after ischemia. Preoperative (day 8), reperfusion 0,3,6 h liver tissue. The protein expression of p-PI3K (p85), p-AKT (ser473), AKT, p-GSK-3β (ser9) and GSK-3β in liver tissues were detected by Western blot. Results: The protein expression of p-PI3K (p85), p-AKT (ser473) and p-GSK-3β (ser9) in OA group were significantly increased compared with the other three groups ); At this time, there was no significant difference between SH group, IR group and CM group (P> 0.05). Compared with the other three groups, the protein levels of p-PI3K (p85), p-AKT (ser473) and p-GSK-3β (ser9) in OA group were significantly increased at 3h and 6h after reperfusion (P < (P <0.05). There was no significant difference in the content of each protein between the IR group and the CM group at the corresponding time point (P> 0.05). The AKT in each group was significantly higher than that in the other three groups GSK-3β protein content in all time points were not statistically different (P> 0.05). Conclusion: OA pretreatment can increase the protein levels of p-PI3K (p85), p-AKT (ser473) and p-GSK-3β (ser9) before and after HIRI and activate the PI3K-AKT-GSK- It is one of the mechanisms of reducing HIRI in OA.