已有报道显示，microRNA-22（miR-22）具有神经保护作用。然而，miR-22在缺血/再灌注（I/R）诱导的脑损伤中的具体作用和机制尚不清楚。本研究通过使用离体氧-葡萄糖剥夺/再灌注（OGD/R）模型评估了miR-22是否参与了I/R诱导的神经元损伤以及其中的潜在机制。结果表明，在OGD/R下，miR-22在SH-SY5Y细胞中明显降低。miR-22的特异性mimic上调能够保护SH-SY5Y细胞免受OGD/R诱导的损伤。荧光素酶报告试验证明，T细胞淋巴瘤浸润和转移1（Tiam1）是miR-22的直接靶标。miR-22的mimic明显抑制了OGD/R暴露的SH-SY5Y细胞中的Tiam1表达。Tiam1小干扰RNA（siRNA）能够减轻OGD/R诱导的SH-SY5Y细胞损伤。此外，Tiam1 siRNA降低了OGD/R暴露的SH-SY5Y细胞中Ras相关C3激动毒素底物1（Rac1）的激活，并且上调Rac1活性能够减轻miR-22上调的神经保护效应。此外，OGD/R暴露导致miR-22甲基化增加，去甲基化剂5-阿扎-2'-脱氧胞苷（5-Aza-dC）显著上调了miR-22的表达，并抑制了Tiam1的表达和Rac1的激活。综上所述，我们的结果表明，DNA甲基化介导的miR-22降低通过促进Tiam1/Rac1信号的激活加重了I/R诱导的神经元损伤。我们的发现深入理解了I/R诱导的脑损伤，同时暗示miR-22可以是该疾病的有希望的治疗靶点。

MicroRNA-22 (miR-22) has been reported to exert a neuroprotective effect. However, the specific role and mechanism of miR-22 in ischemia/reperfusion (I/R)-induced brain injury are still not known well. In this study, we evaluated whether miR-22 participates in I/R-induced neuronal injury and the potential mechanism by using an oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro. Our results showed that miR-22 was significantly down-regulated in SH-SY5Y cells suffering from OGD/R. Up-regulation of miR-22 by its specific mimic could protect SH-SY5Y cells against OGD/R-induced injury. The luciferase reporter assay demonstrated that T-cell lymphoma invasion and metastasis 1 (Tiam1) was a direct target of miR-22. MiR-22 mimic obviously inhibited Tiam1 expression in OGD/R-exposed SH-SY5Y cells. Tiam1 siRNA could attenuate OGD/R-induced SH-SY5Y cell injury. In addition, Tiam1 siRNA reduced the activation of Ras-related C3 botulinum toxin substrate 1 (Rac1) in OGD/R-exposed SH-SY5Y cells, and up-regulation of Rac1 activity could attenuate the neuroprotective effect of miR-22 up-regulation. Furthermore, OGD/R exposure led to increased methylation of miR-22, and the demethylating agent 5-Aza-dC significantly up-regulated miR-22 expression and inhibited Tiam1 expression and Rac1 activation. Taken together, our results demonstrated that DNA methylation-mediated miR-22 down-regulation aggravated I/R-induced neuron injury by promoting the activation of Tiam1/Rac1 signals. Our findings provide a deeper understanding of I/R-induced brain injury and suggest that miR-22 may be a promising therapeutic target for this disease.