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

Effect of Emodin on PI3K/Akt/Mtor Signaling Pathway in Hippocampus of Schizophrenic Rats

目的:探讨大黄素调节磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路对精神分裂症(SP)大鼠神经损伤及认知功能的影响。方法:通过注射地卓西平(MK-801)建立SP大鼠模型,并将正常大鼠为对照组,SP大鼠随机分为SP组、不同剂量(20、40、60mg/kg)大黄素组、60mg/kg大黄素+LY294002组,刻板行为及共济失调评分标准评价大鼠行为学功能;Morris水迷宫实验评估大鼠认知功能;试剂盒检测脑组织乙酰胆碱酯酶(AchE)、乙酰胆碱(Ach)活性;HE检测海马组织病理学变化;qRT-PCR检测脑组织中脑源性神经营养因子(BDNF)mRNA、钙依赖性蛋白激酶(CaMKⅡ)mRNA表达;Western blot检测PI3K/Akt/mTOR通路相关蛋白表达。结果:与对照组相比,SP组穿越平台次数、Ach活性、BDNF mRNA、CaMKⅡmRNA表达、p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR表达显著降低,刻板行为及共济失调评分、平均逃避潜伏期、AchE活性显著增加(P<0.05);但不同剂量大黄素干预后,穿越平台次数、Ach活性、BDNF mRNA、CaMKⅡmRNA表达、p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR表达显著增加,刻板行为及共济失调评分、平均逃避潜伏期、AchE活性显著降低,组间有差异(P<0.05);60mg/kg大黄素联合LY294002较60mg/kg大黄素组穿越平台次数、Ach活性、BDNF mRNA、CaMKⅡmRNA表达、p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR表达显著降低,刻板行为及共济失调评分、平均逃避潜伏期、AchE活性显著增加(P<0.05)。结论:大黄素通过调节PI3K/Akt/mTOR信号通路改善SP大鼠认知能力,发挥神经保护功能。

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,CaMKⅡmRNA,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,CaMKⅡmRNA,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,CaMKⅡmRNA,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.