ABSTRACT

This work aimed to assess the role of TLR8 in cerebral I/R injury and its in-depth pathogenesis. Bioinformatics analysis indicated that TLR8 was up-regulated in patients with ischemic stroke than that in healthy control, and miR-18a-5p was the upstream regulatory of TLR8. Then, the rat pheochromocytoma PC12 cells were exposed in oxygen-glucose-deprivation/reoxygenation (OGD/R) conditions to construct a model in vitro. The functional experiments indicated that OGD/R can decline the viability and elevate the apoptosis of PC12 cells, while up-regulation of miR-18a-5p can alleviate OGD/R-induced cell injury. Notably, overexpression of TLR8 reverses the miR-18a-5p-mediated protection on OGD/R-induced cells injury. Finally, we found that up-regulation of miR-18a-5p obviously declined the protein levels of TLR4 and TLR7 as well as the phosphorylation of NF-κB, while overexpression of TLR8 canceled the decrease caused by miR-18a-5p up-regulation. In summing, our results illustrated that miR-18a-5p/TLR8 axis can mitigate OGD/R-induced cells injury through TLRs and NF-κB pathway.

摘要

这项工作旨在评估TLR8在脑I / R损伤中的作用及其深入的发病机理。生物信息学分析表明，缺血性中风患者的TLR8较健康对照者上调，而miR-18a-5p是TLR8的上游调控因子。然后，将大鼠嗜铬细胞瘤PC12细胞暴露于氧葡萄糖剥夺/复氧（OGD / R）条件下，以体外建立模型。功能实验表明，OGD / R可以降低PC12细胞的活力并提高其凋亡，而miR-18a-5p的上调可以减轻OGD / R引起的细胞损伤。值得注意的是，TLR8的过表达逆转了miR-18a-5p介导的对OGD / R诱导的细胞损伤的保护作用。最后，我们发现miR-18a-5p的上调明显降低了TLR4和TLR7的蛋白水平以及NF-κB的磷酸化，而TLR8的过表达抵消了miR-18a-5p上调引起的下降。 。总之，我们的结果表明，miR-18a-5p / TLR8轴可通过TLR和NF-κB途径减轻OGD / R诱导的细胞损伤。