microRNA转染的骨髓间充质干细胞对脑出血大鼠神经功能恢复机制的研究

Bone marrow-derived mesenchymal stem cells (BM-MSCs) transplantation can promote the neurological recovery of intracerebral hemorrhage rats, and microRNAs play an important regulatory role on BM-MSCs. To explore the possible mechanisms of microRNA transfected BM-MSCs promoting the neurological recovery in intracerebral hemorrhage rats, GFP labelled BM-MSCs would be transfected with miR-21 mimics and miR-126 mimics respectively. ①In vitro, the bcl-2 expression of miR-21 transfected BM-MSCs, anti-apoptotic ability of co-cultured primary hippocampal neurons will be observed，and the VEGF expression of miR-126 transfected BM-MSCs and the neoangiogenesis ability of co-cultured vascular endothelial cells will be observed. ②In vivo, miR-21 transfected BM-MSCs and miR-126 transfected BM-MSCs would be injected into the vein artery of cerebral hemorrhage rats respectively. Then the anti-apoptotic ability and neoangiogenesis ability of perihematomal cells will be determined. Additionally, neurological scores of rats will be evaluated. Our study can provide a new theoretical base for BM-MSCs transplantation to intracerebral hemorrhage.

骨髓间充质干细胞(BM-MSCs)移植治疗可有效促进脑出血大鼠的神经功能恢复，microRNA对于骨髓间充质干细胞有广泛的调控作用。为了探讨microRNA在脑出血大鼠BM-MSCs移植治疗中有关神经功能恢复的可能机制，本研究拟将miR-21和miR-126模拟物分别转染至GFP标记的大鼠BM-MSCs：①在体外实验中，观察miR-21转染组BM-MSCs的Bcl-2表达水平，并评价与之共培养的海马神经元细胞的抗凋亡能力；观察miR-126转染组BM-MSCs的VEGF表达水平，并评价与之共培养的血管内皮细胞的血管再生能力。②在体内实验中，分别将miR-21转染组、miR-126转染组以及未转染microRNA组BM-MSCs经鼠尾静脉注射至脑出血大鼠体内，观察大鼠血肿灶周组织细胞的抗凋亡和血管再生能力，并且对大鼠进行神经功能评分。以期为脑出血BM-MSCs移植治疗提供新的理论依据。

骨髓间充质干细胞(BM-MSCs)移植治疗可有效促进脑出血(ICH)大鼠的神经功能恢复，microRNA对于骨髓间充质干细胞有广泛的调控作用。为了探讨microRNA在脑出血大鼠BM-MSCs移植治疗中有关神经功能恢复的可能机制，我们做了一系列体外实验和体内实验，结果表明：(1)miR-21可以有效改善BM-MSCs对ICH大鼠的神经功能评分，显著提高BM-MSCs在ICH大鼠脑内的存活率，抑制血肿周围神经元凋亡，miR-21通过与TRPM7的靶向结合，从而发挥神经保护作用；(2)miR-23b通过靶向IPMK抑制神经炎症而在ICH中发挥保护作用，其机制可能与调控Akt/mTOR自噬途径有关；(3)miR-152可以通过靶向抑制TXNIP介导的NLRP3炎症小体的激活，改善大鼠脑出血后的神经炎症和脑损伤情况。这些研究成果可能为脑出血的治疗带来新的策略。