外泌体内microRNA-135a跨血脑屏障转运的初步研究  

A preliminary study on the cross blood-brain-barrier transport of exosomal microRNA-135a

作　　者：刘辰庚[1] 郝婷 杨婷婷[1] 孟双[3] 王培昌[1] 

机构地区：[1]首都医科大学宣武医院检验科,北京100053 [2]山东省菏泽市立医院病理科,山东菏泽274000 [3]中国疾病预防控制中心传染病预防控制所传染病预防控制国家重点实验室,北京102206

出　　处：《中国医药导报》2017年第33期22-25,30,共5页China Medical Herald

基　　金：国家自然科学基金青年基金项目(81401734);北京市医院管理局"青苗"计划专项经费资助项目(QML20150804)

摘　　要：目的初步研究外泌体内micro RNA-135a(miR-135a)跨血脑屏障和细胞转运的现象。方法提取APP/PS1双转基因小鼠脑脊液(CSF)的高miR-135a外泌体,将其注射入野生型小鼠脑室并干预SH-SY5Y细胞,检测小鼠外周血和培养基外泌体内miR-135a水平及SH-SY5Y细胞β分泌酶-1(BACE-1)的表达和活性。结果高miR-135a外泌体脑室注射能使野生型小鼠CSF和血浆外泌体miR-135a显著升高(P<0.05);经APP/PS1双转基因小鼠CSF源外泌体干预的SH-SY5Y细胞,其细胞内的miR-135a含量显著高于其他干预组和对照组(P<0.05);SH-SY5Y细胞的BACE-1活性显著降低(P<0.05),且其m RNA表达水平的变化趋势与活性变化趋势一致。结论外泌体可将脑脊液中的"高miR-135a"这一生物信号跨越血脑屏障传递至外周血,这为将血浆外泌体miR-135a作为阿尔茨海默病诊断生物标志物提供了更坚实的实验依据。Objective To study the effect of microRNA-135a （miR-135a） on blood-brain barrier and cell transport in exocrine. Methods The high miR-135a exosomes were extracted from the cerebrospinal fluid （CSF） of the transgenic mice and injected into the ventricles of the wild type mice and intervened with SH-SY5Y cells. The levels of miR-135a in the peripheral blood of mice and the exosomes of the culture, and the expression and activity of β-secretase-1 （BACE-1） in SH-SY5Y cells were determined. Results Intraventricular injection of miR-135a exosomes resulted in a significant increase in CSF and plasma exosomal miR-135a in wild-type mice （P 〈 0.05）. The activity of BACE-1 in SH-SY5Y cells treated with exosomes harvest from the CSF of APP/PS1 double transgenic mice was significantly lower than that in other intervention group and control group （P 〈 0.05）, and the mRNA expression level of SH-SY5Y cells was significantly lower than that of control （P 〈 0.05）. The trend of change is consistent with the trend of activity. Conclusion The signal of ＂high miR-135a＂ can be transferred from CSF to blood through the blood-brain barrier, which provides a more solid experimental basis for the use of exosomal miR-135a as a biomarker of Alzheimer＇s disease.

关 键 词：阿尔茨海默病 MICRORNA 外泌体 

分 类 号：R749[医药卫生—神经病学与精神病学]