Objective To investigate the role of PI3K/AKT/GSK-3βsignaling pathway in uric acid,glucose and lipid metabolism in rats with hyperuricemia(HUA).Methods Forty SD rats were randomly divided into 4 groups,of which 2 groups were unmodeled SD rats,namely model control group(C group)and LY294002 group(L group);the remaining 2 groups were modeled successfully SD rats,which were divid-ed into hyperuricemia group(H group)and hyperuricemia plus LY294002 intervention group(HL group).The rats in the C group were given distilled water(10 mL/kg)orally and intraperitoneally injec-ted with 0.2％DMSO solution(6 mL/kg)daily.The rats in the L group received the same dose of dis-tilled water and intraperitoneally injected LY294002 solution(6 mL/kg).The rats in the H group were administered adenine(100 mg/kg)and ethambutol(250 mg/kg)orally daily.The rats in the HL group were given the same dose of adenine and ethambutol along with daily intraperitoneal injection of LY294002 solu-tion(6 mL/kg).The intervention lasted for 15 days,during which blood samples were collected from the orbital venous plexus every 3 days to measure serum uric acid(UA),serum creatinine(Scr),blood urea nitrogen(BUN),glucose(GLU),triglycerides(TG)and total cholesterol(TC).On the 15th day,kid-ney tissues were collected after anesthesia,and the expression levels of PI3K,AKT and GSK-3β in renal tissues were detected using quantitative real-time PCR and Western blotting.Results Before the experi-ment,there were no significant differences in serum UA,Scr,BUN,GLU,TG and TC levels among the C group,L group,H group and HL group.(P＜0.05).After the experiment,UA,Scr and BUN levels in the H and HL groups were higher than those in the C and L groups.Compared with the C group on the 6th day,UA levels in the H and HL groups decreased but increased from the 9th to the 15th day,with significant differences(P＜0.05).GLU levels in the L,H,and HL groups were higher than those in the C group,with the L group showing higher GLU levels than the C group on the 12th day,and the H and HL groups showing higher GLU levels than the L group on the 6th day(P＜0.05).TC and TG levels in the H and HL groups were higher than those in the C and L groups,with TG levels in the HL group being higher than those in the H group on the 9th day(P＜0.05).Quantitative real-time PCR results showed that PI3K,AKT and GSK-3β expression levels were significantly higher in the H and HL groups compared to the C group(P＜0.05).In the L group,AKT expression was decreased,while GSK-3β was increased compared to C group(P＜0.05).Compared to L group,PI3K,AKT and GSK-3β levels were significantly higher in the H and HL groups(P＜0.05).Compared to H group,PI3K,AKT and GSK-3β levels were significantly higher in the HL group(P＜0.05).Western blot results also indicated significantly increased the levels of PI3K,AKT and GSK-3β in the H and HL groups compared to the C group(P＜0.05),and higher levels in the HL group compared to the H group(P＜0.05).Conclusion There may be a potential link between the PI3K/AKT/GSK-3β signaling pathway and HUA,suggesting the importance of this pathway in future therapeutic and preventive strategies.
hyperuricemia(HUA)uric acidPI3K/AKT/GSK-3β signaling pathwaymetabolismthe mechanism of action
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