Abstract:Objective: To investigate the impact of emodin on neurological injury and cognitive function in rats with schizophrenia (SP) by regulating the phosphatidylinositol3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway.Methods: An SP rat model was established by injecting dexamethasone (MK-801), and normal rats were used as the control group. SP rats were randomly included in the SP group, different doses (20, 40, 60mg/kg) of emodin groups, and 60mg/kg of emodin+LY294002 group. Stereotypic behavior and ataxia scoring criteria were applied to evaluate rat behavioral function. Morris water maze experiment was applied to evaluate cognitive function in rats. Reagent kits were applied to detect acetylcholinesterase (AchE) and acetylcholine (Ach) activities in brain tissue. HE was applied to detect pathological changes in hippocampal tissue. QRT-PCR was applied to detect the expression of brain-derived neurotrophic factor (BDNF) mRNA and calcium-dependent protein kinase (CaMK II) mRNA in brain tissue. Western blot was applied to detect the expression of PI3K/Akt/mTOR pathway-related proteins.Results: Compared with the control group, the number of platform crossings, Ach activity, the expression of BDNF mRNA, CaMK Ⅱ mRNA, the expression of p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR were greatly reduced in the SP group, the stereotypes and ataxia scores, average avoidance latency, and AchE activity were greatly increased (P<0.05). However, after intervention with different doses of emodin, the number of platform crossings, Ach activity, the expression of BDNF mRNA, CaMK Ⅱ mRNA, the expression of p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR were greatly increased, the stereotypes and ataxia scores, average avoidance latency, and AchE activity were greatly reduced, with differences between groups (P<0.05). The number of platform crossings, Ach activity, the expression of BDNF mRNA, CaMK Ⅱ mRNA, the expression of p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR in 60mg/kg emodin + LY294002 group were greatly lower than 60mg/kg emodin group, the stereotypes and ataxia scores, average avoidance latency, and AchE activity were greatly increased (P<0.05).Conclusion: Emodin can improve the cognitive ability and neuroprotective function of SP rats by regulating PI3K/Akt/mTOR signaling pathway.
王德佳, 杨波. 大黄素对精神分裂症大鼠海马组织PI3K/Akt/mTOR信号通路的影响[J]. 河北医学, 2024, 30(9): 1446-1451.
WANG Dejia, YANG Bo. Effect of Emodin on PI3K/Akt/Mtor Signaling Pathway in Hippocampus of Schizophrenic Rats. HeBei Med, 2024, 30(9): 1446-1451.
[1] Niu J,Cao Y,Ji Y.Resveratrol,a SIRT1 activator,ameliorates MK-801-induced cognitive and motor impairments in a neonatal rat model of schizophrenia[J].Front Psychiatry,2020,11(1):716-724. [2] Landreth K,Burgess M,Watson L,et al.Handling prevents and reverses cognitive deficits induced by sub-chronic phencyclidine in a model for schizophrenia in rats[J].Physiol Behav,2023,263(1):114117-114126. [3] Saha P,Ahmad F.Neuroprotective,anti-inflammatory and antifibrillogenic offerings by emodin against alzheimer's dementia:a systematic review[J].ACS Omega,2024,9(7):7296-7309. [4] Nawwar DA,Zaki HF,Sayed RH.Role of the NRG1/ErbB4 and PI3K/AKT/mTOR signaling pathways in the anti-psychotic effects of aripiprazole and sertindole in ketamine-induced schizophrenia-like behaviors in rats[J].Inflammopharmacology,2022,30(5):1891-1907. [5] Pan B,Xu L,Weng J,et al.Effects of icariin on alleviating schizophrenia-like symptoms by regulating the miR-144-3p/ATP1B2/mTOR signalling pathway[J].Neurosci Lett,2022,791(1):136918-136927. [6] Tao X,Yan M,Wang L,et al.Effects of estrogen deprivation on memory and expression of related proteins in ovariectomized mice[J].Ann Transl Med,2020,8(6):356-367. [7] 钟海龙,江熏英,何著发,等.奥氮平对精神分裂症大鼠认知功能和神经元损伤影响中PI3K/Akt信号通路的作用[J].解剖学报,2022,53(6):719-726. [8] Gao LL,Wang ZH,Mu YH,et al.Emodin promotes autophagy and prevents apoptosis in sepsis-associated encephalopathy through activating BDNF/TrkB signaling[J].Pathobiology,2022,89(3):135-145. [9] Xian YF,Ip SP,Li HQ,et al.Isorhynchophylline exerts antidepressant-like effects in mice via modulating neuroinflammation and neurotrophins:involvement of the PI3K/Akt/GSK-3β signaling pathway[J].FASEB,2019,33(9):10393-10408. [10] Yang CZ,Wang SH,Zhang RH,et al.Neuroprotective effect of astragalin via activating PI3K/Akt-mTOR-mediated autophagy on APP/PS1 mice[J].Cell Death Discov,2023,9(1):15-27. [11] 钟鸣,刘传朋,邱炳杰,等.奥氮平通过PI3K/Akt通路对精神分裂症模型大鼠发挥神经保护作用的研究[J].中国医院用药评价与分析,2020,20(5):554-558.