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

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.