电针对创伤后应激障碍小鼠前额叶皮质磷脂酰肌醇和溶血磷脂酰肌醇的影响

The impact of electroacupuncture on the composition of phosphatidylinositol and lysophosphatidylinositol in prefrontal cortex of mice models with posttraumatic stress disorder

目的探讨电针(EA)干预对创伤后应激障碍(PTSD)小鼠前额叶皮质(PFC)磷脂酰肌醇(PI)和溶血磷脂酰肌醇(LPI)的影响。方法将24只雄性C57BL/6小鼠随机分为对照组、模型组(PTSD)和电针治疗组(EA+PTSD)。经适应性饲养后,模型组和电针治疗组均接受单次延长应激造模,造模后在小鼠百会穴分别给予电针刺激或假电针刺激。在最后一次电针干预结束后7 d进行行为学检测,之后处死小鼠,取PFC进行脂质组学分析,比较各处理组PI和LPI含量的差异,并分析差异脂质分子与行为学的相关关系。结果模型组开臂停留时间低于对照组和电针治疗组,模型组环境诱发僵直时间和声音诱发僵直时间高于对照组和电针治疗组(P<0.05)。模型组LPI(18∶1)、LPI(18∶0)以及LPI总含量均低于对照组和电针治疗组(P<0.05);模型组PI(17∶0/20∶4)、PI(18∶2/20∶4)和PI(18∶1/22∶6)的含量均低于对照组(P<0.05),电针治疗组PI(17∶0/20∶4)、PI(16∶0/20∶4)和PI(18∶1/20∶4)的含量均低于对照组(P<0.05)。LPI(18∶1)含量与开臂停留时间呈正相关(P<0.01),与环境诱发僵直时间呈负相关(P<0.05);LPI(18∶0)含量和LPI总含量均与开臂停留时间呈正相关(P<0.05)。结论PTSD模型小鼠前额叶皮质LPI水平降低,电针在缓解PTSD样行为的同时,也上调了其前额叶皮质的LPI水平。

Objective Posttraumatic stress disorder(PTSD)refers to the delayed and persistent stress disorder that occurs after an individual experiences,witnesses or encounters a major,unusual,life threatening and health threatening catastrophic event,mainly manifested in a series of emotional and behavioral reactions of the victims,such as avoidance,flashback,increased alertness,etc.In recent years,the outbreaks of COVID-19(Corona Virus Disease 2019),local wars,economic crisis and other major events have had a huge impact on people’s life and work,and the prevalence of PTSD has increased significantly,bringing a heavy burden of disease to individuals,families and society.Prefrontal cortex(PFC)is one of the key brain regions regulating stress response,and its structural and functional abnormalities play important roles in the pathogenesis of PTSD.The neural network composed of the PFC,hippocampus and amygdala can regulate the process of fear learning and memory,thereby regulating emotional responses.The amygdala is critical for the formation of fear-related associations and the expression of emotional behaviors in response to impending threats,and these processes are regulated by projections from brain regions such as the hippocampus,dorsolateral PFC,dorsolmedial PFC,and ventromedial PFC.Electroacupuncture(EA)is a modified form of traditional acupuncture,which can not only improve the emotional symptoms in patients with anxiety and depression,but also improve the related symptoms of PTSD.Its main mechanism may be the regulation of the function and structure of PFC.Phosphatidylinositol(PI)is a major component of cell membrane and inner mitochondrial membrane,which is involved in membrane transport,membrane signal transduction and regulation of cytoskeleton dynamics.Lysophosphatidylinositol(LPI)is one of the main metabolites of PI,which plays an important role in oxidative stress,apoptosis and inflammation.Studies have found that the levels of PI and LPI in blood or brain tissue of patients with various mental disorders,such as depression and bipolar disorder,are abnormal and correlated with the severity of symptoms.The levels of PI and LPI in prefrontal cortex were down-regulated in depressed rats.Therefore,does EA stimulation act by modulating PI and LPI expression levels in prefrontal cortex in animal models of PTSD?This study aims to investigate the effects of EA intervention on PI and LPI in PFC of PTSD mice by constructing PTSD mice models with modified single prolonged stress(mSPS),providing a new idea for further elucidating the molecular biological mechanism of EA in treating PTSD.Methods A total number of 24 C57BL/6 mice were randomly divided into control group,model(PTSD)group and EA treatment(EA+PTSD)group.After adaptive feeding,both the PTSD group and EA+PTSD group received mSPS.Then mice in EA+PTSD group received EA whereas mice in control group and PTSD group received sham EA(acupuncture without electricity),which was given to stimulate Baihui Point with stimulation parameters:2/15 Hz,1 mA density wave,stimulation for 30 min/d for 7 consecutive days.Behavioral tests,such as elevated plus maze and fear box,were carried out 7 days after the end of the last EA treatment,and then the mice were killed.The PFC was separated for lipidomic analysis.The compositions of PI and LPI in the PFC of each group were analyzed,and the correlation between the concentration of PI and LPI and behaviors was also observed.Results The open arm residence time in PTSD group was significantly lower than those in control groupand EA+PTSD group,and the times of environment-induced stiffness and sound-induced stiffness in PTSD group were significantly increased when compared with those in EA+PTSD group and control group(P<0.05).The contents of LPI(18∶1),LPI(18∶0)and total LPI in PTSD group were decreased when compared with those in control group and EA+PTSD group(P<0.05).The contents of PI(17∶0/20∶4),PI(18∶2/20∶4)and PI(18∶1/22∶6)in PTSD group were decreased when compared with those in control group(P<0.05).The contents of PI(17∶0/20∶4),PI(16∶0/20∶4)and PI(18∶1/20∶4)in EA+PTSD group were decreased when compared with those in control group(P<0.05).The content of LPI(18∶1)was positively correlated with open arm residence time(P<0.01),and negatively correlated with environment-induced stiffness time(P<0.05);the content of LPI(18∶0)and total LPI were positively correlated with open arm residence time(P<0.05).Conclusion The level of LPI in the PFC decreases in mice models with PTSD.EA may not only alleviate PTSD-like behaviors,but also increase the level of LPI in the PFC.