解郁丸对注意缺陷多动共患焦虑障碍模型大鼠AKT/GSK-3β/β-catenin通路的影响OA

Objective:To investigate the protective effects and mechanisms of Jieyu Pills(解郁丸)on a rat model of attention deficit hyperactivity disorder(ADHD)comorbid with anxiety disorder.Methods:A rat model of ADHD comorbid with anxiety disorder was established in spontaneously hypertensive rats(SHRs)using chronic restraint stress.Thirty-six SHRs were randomly divided into a model control group,a methylphenidate hydrochloride group(5.4 mg/kg),a Jingling Oral Liquid group(5.98 mL/kg),and Jieyu Pills 0.7,1.3,and 2.7 g/kg groups.Six Wistar-Kyoto(WKY)rats served as a normal control group.All treatments were administered daily via intragastric administration for 14 consecutive days.After the final administration,behavioral assessments were conducted using the Morris water maze,open field test,and el-evated plus maze test.Dopamine(DA)and serotonin(5-HT)levels in the prefrontal cortex,striatum,and serum were measured by enzyme-linked immunosorbent assay(ELISA).Western blot and real-time PCR were employed to assess the protein and mRNA expression levels of key components in the AKT/GSK-3β/β-catenin signaling pathway in the pre-frontal cortex and striatum.Results:Compared with the normal control group,the model group exhibited a significant in-crease in the number of effective crossings(P<0.05)and reduced escape latency(P<0.01)in the Morris water maze,along with prolonged movement duration and distance in the open field test(P<0.01).The levels of DA and 5-HT in the prefrontal cortex,striatum,and serum significantly decreased(P<0.01).Protein expression levels of p-AKT/AKT,p-GSK-3β/GSK-3β,and β-catenin/β-actin in the prefrontal cortex and striatum were markedly downregulated(P<0.05 or P<0.01),the mRNA expression levels of Akt and β-catenin were significantly downregulated(P<0.05 or P<0.01),while the expression of Gsk3β mRNA was upregulated(P<0.05 or P<0.01).Compared with the model control group,the Jieyu Pills 2.7 g/kg group showed a significant increase in the number of effective crossings(P<0.01)and short-ened escape latency(P<0.05)in the Morris water maze,as well as reduced movement duration and distance in the open field test(P<0.01).The elevated plus maze test revealed significantly decreased percentages of time spent and entries into the closed arms(P<0.05 or P<0.01).DA and 5-HT levels in the prefrontal cortex,striatum,and serum were sig-nificantly elevated(P<0.05 or P<0.01).Protein expression levels of p-AKT/AKT,p-GSK-3β/GSK-3β,and β-cate-nin/β-actin were upregulated(P<0.05 or P<0.01),the mRNA expression levels of Akt and β-catenin were upregulated(P<0.05 or P<0.01),while Gsk3β mRNA expression was significantly downregulated(P<0.01).Conclusion:Jieyu Pills ameliorate cognitive deficits in a rat model of ADHD comorbid with anxiety model rats by modulating the expression of the AKT/GSK-3β/β-catenin signaling pathway in the prefrontal cortex and striatum.It enhances the expression of re-lated proteins and mRNAs in this signaling pathway,inhibits GSK-3β activity to reduce β-catenin degradation,and pre-vents endoplasmic reticulum stress.