TLR4/MyD88在单一延长应激诱导的PTSD大鼠海马中的表达及意义  

Expression and role of TLR4/MyD88 in the hippocampus of rats with post‐traumatic stress disorder induced by single prolonged stress

作　　者：赵亚楠 黄德盛 陈云 孙艺瑶 覃伟林 谢菊华 ZHAO Yanan;HUANG Desheng;CHEN Yun(Department of Histology and Embryology,Shenyang Medical College,Shenyang 110034,China)

机构地区：[1]沈阳医学院组织胚胎学教研室,辽宁沈阳110034

出　　处：《中风与神经疾病杂志》2023年第11期1021-1024,共4页Journal of Apoplexy and Nervous Diseases

基　　金：沈阳市“高层次创新人才计划”项目(RC190477);沈阳医学院科学研究基金项目(20181005、20171005);沈阳医学院2021年校级大学生科研项目(20219051)。

摘　　要：目的探讨TLR4/MyD88在单一延长应激诱导的创伤后应激障碍(PTSD)大鼠海马中的表达及意义。方法将Wistar大鼠30只(n=45只)随机分为:健康对照组15只、PTSD组30只(分造模后4 d组、造模后7 d组各15只)。PTSD组采用国际公认的单一延长应激(single-prolonged stress,SPS)诱导形成创伤后应激障碍。采用Morris水迷宫检测两组大鼠空间记忆能力,采用尼氏染色观察两组大鼠海马形态改变,并通过Western blotting检测两组大鼠海马组织中TLR4、MyD88蛋白及其下游NF-κB蛋白的表达。结果与健康对照组比较,PTSD组平均潜伏期延长(P<0.05);尼氏染色示PTSD组大鼠海马神经元排列稀疏、染色浅淡,胞浆中尼氏体分布明显减少。同时Western blotting检测示大鼠经SPS刺激后4 d、7 d TLR4、MyD88及其下游NF-κB蛋白表达均明显增加,且与对照组有统计学差异(P<0.05)。结论单一延长应激可致大鼠空间记忆功能受损,这可能与其海马TLR4/MyD88/NF-κB上调有关。TLR4/MyD88信号通路激活可能是单一延长应激模拟PTSD过程中海马损伤的重要分子机制之一。Objective To explore the expression and role of Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)in the hippocampus of a rat model of post‐traumatic stress disorder(PTSD)induced by single prolonged stress(SPS).Methods Forty-five rats were randomly assigned into control group(n=15)or PTSD group(n=30;15 each were examined on days 4 and 7 after modeling,respectively).PTSD was induced by SPS,which was recognized internationally.The Morris water maze test was carried out to measure the spatial memory of the rats.The morphological changes of the hippocampus were examined with Nissl staining.The expression of TLR4,MyD88,and downstream nuclear factor-kappa B(NF-κB)was determined by Western blot.Results Compared with the control group,the PTSD group showed a significantly prolonged mean escape latency(P<0.05);sparsely arranged and lightly stained neurons and a reduced number of Nissl bodies within cytoplasm in the hippocampus;and significantly increased protein expression of TLR4,MyD88,and NF-κB on days 4 and 7 after SPS stimulation(all P<0.05).Conclusion SPS can impair the spatial memory of rats,which may be associated with the up-regulation of TLR4/MyD88/NF-κB in the hippocampus.The activation of TLR4/MyD88 signaling may be one of important molecular mechanisms in the development of SPS-induced PTSD.

关 键 词：创伤后应激障碍 单一延长应激 海马 TLR4 MYD88 

分 类 号：R749.12[医药卫生—神经病学与精神病学]