PKH67标记的外泌体源性miR-137在卒中后抑郁治疗中作用的研究

随着对miRNAs和对卒中后抑郁（PSD）发病机制的认识，miRNA靶向治疗成为研究PSD治疗的新焦点，有研究表明miR-137通过抑制Grin2A表达参与抑郁过程。前期研究中，我们发现PSD患者外周血外泌体内的miR-137表达异常，因此我们推测，外泌体源性miR-137可能通过抑制Grin2A表达，促进海马神经再生从而发挥抗抑郁作用。本课题通过生物信息学预测、qRT-PCR、western blot、双荧光素酶报告实验、PKH67荧光标记、以及PET扫描等手段对miR-137的靶基因Grin2A、外泌体miR-137抑制Grin2A的表达、神经干细胞转染miR-137、提取外泌体植入PSD大鼠行为学检测等进行逐步验证。揭示了外泌体miR-137通过抑制Grin2A促进海马神经再生从而发挥抗抑郁作用，为PSD的诊断和miRNA靶向治疗提供更多理论依据。

MiRNA targeting therapy has become a new focus on anti-depression with the understanding of miRNAs and the pathogenesis of post-stroke depression, and previous studies indicated that miR-137 played a role in the depression process by inhibiting Grin2A expression. In the previous study, we found that abnormal expression of miR-137 in serum exosomes of PSD patients. Therefore, we speculate that exosomal miR-137 may promote the regeneration of hippocampal neurons by inhibiting the expression of Grin2A. In our study, bioinformatics prediction, qRT-PCR, western blot, dual luciferase reporter assay, PKH67- labeling and PET were used to verify miR-137 targeting Grin2A, exosomal miR-137 inhibiting the expression of Grin2A, neural stem cells transfected with miR-137, exosome implantation, behavioral evaluation of PSD model and so on. We found that exosomal miR-137 promoted the regeneration of hippocampal neurons by inhibiting the expression of Grin2A, providing more evidence for diagnosis and miRNA targeting therapy for PSD.