Department of Infection, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Infection, The Second Affiliated Hospital of Yichun University, Yichun, China.
Bioengineered. 2022 Mar;13(3):6839-6855. doi: 10.1080/21655979.2022.2038448.
microRNAs, as small endogenous RNAs, influence umpteen sophisticated cellular biological functions regarding neurodegenerative and cerebrovascular diseases. Here, we interrogated miR-381-3p's influence on BV2 activation and neurotoxicity in ischemic and hypoxic environment. Oxygen-glucose deprivation (OGD) was adopted to induce microglial activation and HT-22 neuron damage. Quantitative polymerase chain reaction (qRT-PCR) was taken to check miR-381-3p expression in OGD-elicited BV2 cells and HT-22 neurons. It transpired that miR-381-3p expression was lowered in BV2 cells and HT-22 cells elicited by OGD. miR-381-3p up-regulation remarkably hampered inflammatory mediator expression in BV2 cells induced by OGD and weakened HT22 neuron apoptosis. , miR-381-3p expression was abated in HI rats' ischemic lesions, and miR-381-3p up-regulation could ameliorate inflammation and neuron apoptosis in their brain. C-C chemokine receptor type 2 (CCR2) was identified as the downstream target of miR-381-3p, and miR-381-3p suppressed the CCR2/NF-κB pathway to mitigate microglial activation and neurotoxicity. Therefore, we believed that miR-381-3p overexpression exerts anti-inflammation and anti-apoptosis in ischemic brain injury by targeting CCR2.
微小 RNA（miRNAs）作为小型内源性 RNA，影响神经退行性和脑血管疾病中无数复杂的细胞生物学功能。在这里，我们研究了 miR-381-3p 在缺血和缺氧环境中对 BV2 激活和神经毒性的影响。采用氧葡萄糖剥夺（OGD）诱导小胶质细胞激活和 HT-22 神经元损伤。采用定量聚合酶链反应（qRT-PCR）检测 OGD 诱导的 BV2 细胞和 HT-22 神经元中 miR-381-3p 的表达。结果表明，OGD 诱导的 BV2 细胞和 HT-22 细胞中 miR-381-3p 的表达降低。miR-381-3p 的上调显著抑制了 OGD 诱导的 BV2 细胞中炎症介质的表达，并减弱了 HT22 神经元的凋亡。miR-381-3p 在 HI 大鼠缺血性病变中的表达降低，miR-381-3p 的上调可以改善其大脑中的炎症和神经元凋亡。C-C 趋化因子受体 2（CCR2）被鉴定为 miR-381-3p 的下游靶标，miR-381-3p 抑制 CCR2/NF-κB 通路减轻小胶质细胞激活和神经毒性。因此，我们认为 miR-381-3p 通过靶向 CCR2 在缺血性脑损伤中发挥抗炎和抗凋亡作用。
