P2X7受体抑制剂对青春期创伤后应激障碍大鼠行为及肠道菌群的影响  

Effects of P2X7 receptor inhibitors on behaviour and gut microbiota in adolescent rats with post-traumatic stress disorder

作　　者：徐晶晶 王新起 张洋 许旺旺 高进 XU Jingjing;WANG Xinqi;ZHANG Yang;XU Wangwang;GAO Jin(Department of Clinical Psychology,Qilu Hospital(Qingdao),Cheeloo College of Medicine,Shandong University,Qingdao 266035,Shandong,China)

机构地区：[1]山东大学齐鲁医院(青岛)心理科,山东青岛266035

出　　处：《山东大学学报(医学版)》2025年第4期1-9,共9页Journal of Shandong University:Health Sciences

基　　金：山东省自然科学基金(ZR2021MH286)。

摘　　要：目的探讨嘌呤能离子通道型7(purinergic ligand-gated ion channel 7,P2X7)受体抑制剂对青春期创伤后应激障碍(post-traumatic stress disorder,PTSD)大鼠行为及肠道菌群的影响。方法3周龄雄性Wistar大鼠按随机数字表法分为对照组、模型组和抑制剂组。通过单一延长应激和情景恐惧条件反射方法构建PTSD动物模型,并在应激后早期腹腔注射P2X7受体抑制剂亮蓝G进行干预。采用行为学实验评估大鼠行为表现,通过宏基因组绝对定量测序检测粪便菌群变化。结果与模型组相比,P2X7受体抑制剂显著缩短大鼠僵住时间(P=0.0499),增加开放臂停留时间百分比(P=0.004),提升中央区域运动距离和停留时间百分比(P=0.001,P=0.003),以及自发交替正确率(P=0.008)。宏基因组绝对定量测序分析显示,P2X7受体抑制剂显著增加肠道菌群的总丰度(P=0.003),尤其是厚壁菌门(P=0.002)、毛螺菌科(P=0.006)和颤螺菌科(P=0.003)的绝对丰度,并影响脂质代谢、异种生物降解和代谢、辅酶因子和维生素代谢等功能。此外,Spearman相关性分析显示,差异菌群的绝对丰度与PTSD样行为显著相关。结论应激后早期给予P2X7受体抑制剂干预能够显著改善青春期大鼠的PTSD样行为,其作用可能与调节肠道菌群的总丰度、组成及代谢功能有关。Objective To investigate the effects of the purinergic ligand-gated ion channel 7(P2X7)receptor inhibitor on behaviour and gut microbiota in adolescent rats with post-traumatic stress disorder(PTSD).Methods Three-week-old male Wistar rats were randomly assigned to three groups:control group,model group,and inhibitor group.An animal model of PTSD was established using single prolonged stress and contextual fear conditioning.Following stress induction,early intervention was administered via intraperitoneal injection of the P2X7 receptor inhibitor Brilliant Blue G.Behavioural tests were conducted to assess the rats’behaviour and metagenomic absolute quantification sequencing was employed to analyse alterations in the fecal microbiota.Results Compared to the model group,the P2X7 receptor inhibitor significantly reduced freezing time(P=0.0499),increased the percentage of time spent in the open arms(P=0.004),increased both movement distance and time spent in the central area(P=0.001,P=0.003),and improved the accuracy of spontaneous alternation(P=0.008).Analysis of metagenomic absolute quantification sequencing revealed that the P2X7 receptor inhibitor increased the overall abundance of the gut microbiota(P=0.003),particularly the absolute abundances of Bacillota(P=0.002),Lachnospiraceae(P=0.006)and Oscillospiraceae(P=0.003).In addition,metabolic functions including lipid metabolism,biodegradation and metabolism of xenobiotics,and metabolism of cofactors and vitamins were affected.Furthermore,Spearman correlation analysis revealed a significant association between the absolute abundances of the different microbiota and PTSD-like behaviour.Conclusion Early intervention with the P2X7 receptor inhibitor after stress exposure can significantly alleviate PTSD-like behaviour in adolescent rats.These effects may be related to modulation of the overall abundance,composition,and metabolic functions of the gut microbiota.

关 键 词：嘌呤能离子通道型7受体抑制剂 创伤后应激障碍 青春期 肠道菌群 宏基因组绝对定量测序 

分 类 号：R395[哲学宗教—心理学]