Department of Anesthesiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
State Key Laboratory of Military Stomatology &National Clinical Research Center for Oral Diseases &Shaanxi Key Laboratory of Oral Diseases, Department of Anesthesiology, School of Stomatology, Fourth Military Medical University, Xi'an 710032, China.
Sci Rep. 2016 Dec 14;6:38997. doi: 10.1038/srep38997.
Recent studies have demonstrated microRNAs (miRNAs) and proteins are beneficial to axon regeneration, which may be involved in Electroacupuncture (EA) therapy against stroke. In this study, we aimed to determine the pivotal role of PirB in EA-produced rehabilitation against ischemic stroke; and to screen and investigate the potential miRNAs directly regulating PirB expression. The results showed EA treatment enhanced axon regeneration and new projections from the corticospinal tract at 28 d after cerebral ischemic reperfusion injury of rats. Then, we found EA decreased pirb mRNA and PirB protein expression in the penumbra within 28 days after reperfusion. The reduction of PirB expression facilitated neurite outgrowth after oxygen-glucose deprivation injury. The miRNA microarray showed the level of twenty kinds of miRNAs changed in the penumbra after EA administration. The bioinformatics study and luciferase assay verified miR-181b directly regulated pirb mRNA expression. EA increased miR-181b levels in the penumbras, and improved neurobehavioral function rehabilitation through miR-181b direct targeting of pirb mRNA to regulate the expression of PirB, RhoA and GAP43. In conclusion, we provide the first evidence that EA enhances rehabilitation against stroke by regulating epigenetic changes to directly act on its targets, such as the miR-181b/PirB/RhoA/GAP43 axis, which is a novel mechanism of EA therapy.
最近的研究表明,microRNAs(miRNAs)和蛋白质有助于轴突再生,这可能与电针对中风的治疗作用有关。在这项研究中,我们旨在确定PirB 在电针产生的针对缺血性中风的康复中的关键作用;并筛选和研究直接调节 PirB 表达的潜在 miRNAs。结果表明,电针治疗可增强大脑缺血再灌注损伤后大鼠皮质脊髓束的轴突再生和新投射。然后,我们发现电针治疗可在再灌注后 28 天内降低半影区的 pirb mRNA 和 PirB 蛋白表达。PirB 表达的减少促进了氧葡萄糖剥夺损伤后的神经突生长。miRNA 微阵列显示,电针给药后半影区中有二十种 miRNAs 的水平发生变化。生物信息学研究和荧光素酶测定验证了 miR-181b 可直接调节 pirb mRNA 表达。电针增加了半影区中的 miR-181b 水平,并通过 miR-181b 直接靶向 pirb mRNA 来调节 PirB、RhoA 和 GAP43 的表达,从而改善神经行为功能康复。总之,我们提供了第一个证据,表明电针通过调节表观遗传变化直接作用于其靶点,如 miR-181b/PirB/RhoA/GAP43 轴,从而增强中风后的康复,这是电针治疗的一种新机制。