Department of Pharmacy, Yuhuangding Hospital of Yantai, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20 Yuhuangding East Road, Yantai, 264000, Shandong, China.
Department of Neurosurgery, Yuhuangding Hospital of Yantai, the Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20 Yuhuangding East Road, Yantai, 264000, Shandong, China.
Neuromolecular Med. 2020 Dec;22(4):484-492. doi: 10.1007/s12017-020-08599-y. Epub 2020 May 9.
Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality among the world, while the advance of TBI management is rather limited in recent years. The deregulation of microRNAs (miRNAs) has been widely reported in TBI patients and animal models, and certain miRNAs have been identified as the emerging biomarkers of TBI. However, the role of miRNAs in the regulatory mechanism of TBI remains unclear. To demonstrate the effect of miR-146a mimic on TBI-induced neural damages, TBI mouse model was constructed by cortical impact injury (CCI). The chemokine levels were examined by ELISA assays. Behavioral experiments were used to estimate the impact of miR-146a mimics on neurological functions in mice. Western blot assays were performed to demonstrate the protein levels. qRT-PCR assays were utilized to investigate the expression alteration of RNA levels. It was found that miR-146a was upregulated both in brain and serum in TBI mice. miR-146a mimic downregulated inflammatory cytokines secretion in mouse brain. The NF-κB signaling pathway was inhibited by miR-146a mimic. miR-146a treatment attenuated the impact caused by TBI to mouse brain and improve the long-term neurological function. In conclusion, miR-146a mimics ameliorate TBI-related injuries via JNK and NF-κB signaling pathway.
创伤性脑损伤（TBI）是世界上发病率和死亡率的主要原因之一，而近年来 TBI 治疗的进展相当有限。miRNAs（miRNA）的失调在 TBI 患者和动物模型中得到了广泛报道，某些 miRNA 已被确定为 TBI 的新兴生物标志物。然而，miRNA 在 TBI 调节机制中的作用尚不清楚。为了证明 miR-146a 模拟物对 TBI 诱导的神经损伤的影响，通过皮质撞击伤（CCI）构建了 TBI 小鼠模型。通过 ELISA 测定法检查趋化因子水平。行为实验用于评估 miR-146a 模拟物对小鼠神经功能的影响。通过 Western blot 测定法证明蛋白质水平。qRT-PCR 测定法用于研究 RNA 水平的表达变化。结果发现，miR-146a 在 TBI 小鼠的大脑和血清中均上调。miR-146a 模拟物可下调小鼠大脑中炎症细胞因子的分泌。miR-146a 模拟物抑制 NF-κB 信号通路。miR-146a 处理可减轻 TBI 对小鼠大脑的影响，并改善长期神经功能。总之，miR-146a 模拟物通过 JNK 和 NF-κB 信号通路改善 TBI 相关损伤。
