低强度聚焦超声对血管性痴呆大鼠工作记忆的影响及机制探究  

Effects of low-intensity focused ultrasound on working memory and its mechanism in vascular dementia rats

作　　者：杨佳佳 王倩[1] 王发颀 明东 Yang Jiajia;Wang Qian;Wang Faqi;Ming Dong(Academy of Medical Engineering and Translational Medicine,Tianjin University,Tianjin 300072,China;The College of Precision Instruments&Optoelectronics Engineering,Tianjin University,Tianjin 300072,China)

机构地区：[1]天津大学医学工程与转化医学研究院,天津300072 [2]天津大学精密仪器与光电子工程学院,天津300072

出　　处：《神经解剖学杂志》2021年第4期392-398,共7页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(81871517);国家重点研发项目(2017YFB1300302)。

摘　　要：目的:探究低强度聚焦超声刺激(LIFUS)对血管性痴呆(VD)大鼠工作记忆能力的影响,并从内侧前额叶皮层(mPFC)神经细胞存活和突触相关蛋白,如:N-甲基-D-天冬氨酸受体2B(NR2B)、突触素(SYP)重组蛋白、突触后密度蛋白-95(PSD-95)表达方面探讨影响机制。方法:随机将25只成年雄性Wistar大鼠,分为假手术组(sham)和模型组(model)(n=17)。通过双侧颈总动脉结扎手术(2-VO)建VD模型,术后14 d,将手术组存活的12只大鼠随机分为2-VO模型组(2-VO,n=6)和超声治疗组(2-VO+LIFUS,n=6)。2-VO+LIFUS组进行为期2周的超声刺激干预,刺激靶区为双侧mPFC,每天各刺激10 min。刺激参数为:中心频率=0.5 MHz;脉冲重复频率=2.0 kHz;周期数=150。同时sham组和2-VO组施加伪刺激。14 d后,行Y迷宫自发交替任务、延迟-非匹配样本任务,并通过Nissl染色和Western Blot检测mPFC神经细胞的存活及蛋白表达情况。结果:与sham组比较,2-VO组大鼠正确率明显降低,反应时间加长,尼氏体数量和NR2B蛋白的表达均显著下降。与2-VO组比较,2-VO+LIFUS组大鼠的自发交替率、正确率显著升高,反应时间缩短,尼氏体阳性表达数量明显增多,NR2B蛋白的表达升高。结论:LIFUS可明显改善2-VO大鼠的工作记忆功能,可能是与调控大鼠缺血后mPFC细胞存活、突触相关蛋白表达能力有关。Objective: To examine the effects of low-intensity focused ultrasound stimulation (LIFUS) on working memory and medial prefrontal cortex (mPFC) neuronal cell survival and expression of synaptic related protein in vascular dementia (VD) rats. Methods: Adult male Wistar rats (n = 25) were randomly divided into the sham operation group (sham),and model group (model). The operation group underwent bilateral common carotid artery occlusion.Fourteen days after operation,the surviving rats were divided into 2-VO group (model) and 2-VO + LIFUS group (2-VO + LIFUS). For 2-VO + LIFUS group,LIFUS treatment was performed daily for 10 min on each side of mPFC. We used the following parameters: center frequency = 0. 5 MHz;pulse repetition frequency = 2. 0 kHz;the number of cycles= 150. The animals in both sham and 2-VO groups underwent the same procedures including anesthesia but without LIFUS. They were tested with Y maze spontaneous alternation task and delay-mismatched sample task 14 days after intervention. And the cell viability and expression of protein in mPFC were detected by Nissl’s staining and Western Blot.Results: Compared with sham group,the correct rate in 2-VO group was decreased;reaction time increased and the amount of Nissl bodies and the expression of NR2B decreased significantly in mPFC. Compared with 2-VO group,the spontaneous alternation rate and the correct rate of 2-VO + LIFUS group increased;reaction time decreased;the amount of Nissl bodies and the level of NR2B increased. Conclusion: LIFUS could significantly improve the working memory function of rats in VD,which was related to the regulation of mPFC cell survival and protein expression after ischemia.

关 键 词：血管性痴呆 低强度聚焦超声 工作记忆 大鼠 

分 类 号：R749.13[医药卫生—神经病学与精神病学] R445.1[医药卫生—临床医学]