摘要
目的:观察4-苯基丁酸(4-PBA)对创伤后应激障碍(PTSD)大鼠海马神经元内质网应激(ERS)与凋亡的影响,探讨4-PBA改善PTSD大鼠认知能力的机制。方法:36只成年SD大鼠随机分为正常组、PTSD组和4-PBA+PTSD组,每组12只。PTSD组采用单次延长应激(SPS)构建PTSD大鼠模型,4-PBA+PTSD组从造模次日开始每天于固定时间腹腔注射4-PBA(40 mg/kg),连续给药7 d。Morris水迷宫实验检测各组大鼠的学习记忆能力;Western Blot实验检测各组大鼠海马葡萄糖调节蛋白78(GRP78)、CCAAT增强子结合蛋白同源蛋白(CHOP)及B淋巴细胞瘤-2(Bcl-2)、蛋白激酶R样内质网激酶(PERK)-真核翻译起始因子2α(eIF2α)-活化转录因子4(ATF4)信号通路相关蛋白表达的变化。结果:在Morris水迷宫实验中,与对照组比较,PTSD组大鼠学习记忆能力明显减退(P <0.01);与PTSD组比较,4-PBA+PTSD组大鼠学习记忆功能明显改善(P <0.01)。Western Blot实验结果显示,与对照组比较,PTSD组大鼠GRP78、CHOP的表达明显增加(P <0.01),Bcl-2的表达显著性减少(P <0.01),PERK、eIF2α、p-eIF2α表达显著性增加(P <0.05),与PTSD组比较,4-PBA+PTSD组大鼠GRP78、CHOP的表达明显减少(P <0.01),Bcl-2的表达显著性增加(P <0.05),PERK、eIF2α、p-eIF2α表达显著性减少(P <0.05)。结论:4-PBA能够通过激活PERK-eIF2α-ATF4信号通路抑制PTSD大鼠海马神经元的ERS和凋亡,进而改善PTSD大鼠的认知能力。
Objective: To observe the effects of 4-phenylbutyric acid(4-PBA) on endoplasmic reticulum stress and apoptosis in hippocampal neurons of PTSD rats,and to explore the mechanism of 4-PBA improving cognitive ability in PTSD rats.Method: Thirty-six adult SD rats were divided into three groups: control group,PTSD group,and 4-PBA + PTSD group.PTSD rat model was prepared by single prolonged stress(SPS).The rats of 4-PBA + PTSD group were treated by 4-PBAinjection.Morris water maze test was used to detected the learning and memory ability of rats.The expression of GRP78,CHOP,Bcl-2,and PERK-eIF2α-ATF4 pathway-related proteins(PERK,eIF2α,and p-eIF2α) in the rat hippocampus of each group was detected by Western Blot.Results: Compared with control group,the learning and memory ability of PTSD rats decreased significantly(P < 0.01).Compared with the PTSD group,the learning and memory ability was significantly improved in 4-PBA + PTSD group(P < 0.01).The expression of GRP78,CHOP,PERK,eIF2α,and p-eIF2α expression in rat hippocampus of PTSD group was significantly higher than that of control group,while the expression of Bcl-2 was significantly reduced.The expression of GRP78,CHOP,PERK,eIF2α,and p-eIF2α in rat hippocampus in 4-PBA + PTSD group were significantly reduced,the expression of Bcl-2 was significantly increased than that of PTSD group.Conclusion: 4-PBA can inhibit ERS and apoptosis in hippocampal neurons through PERK-eIF2α-ATF4 signaling pathway,and improve cognitive ability of PTSD rats.
作者
林玲
刘国良
高丽
Lin Ling;Liu Guoliang;Gao Li(Department of Physiology,Henan Medical College,Zhengzhou 451191,China;Department of Preventive Medicine,Henan Medical College,Zhengzhou 451191,China)
出处
《神经解剖学杂志》
CAS
CSCD
北大核心
2020年第4期445-449,共5页
Chinese Journal of Neuroanatomy
基金
河南省科技厅自然科学项目(142300410431)
河南省教育厅高等学校重点科研项目(20B180004)。
关键词
创伤后应激障碍
内质网应激
凋亡
海马
4-苯基丁酸
大鼠
post-traumatic stress disorder(PTSD)
endoplasmic reticulum stress(ERS)
apoptosis
hippocampal
4-phenylbutyric acid
rat
