TNFα and microRNA-15b expression changes in experimental model of subarachnoid haemorrhage

CESKA A SLOVENSKA NEUROLOGIE A NEUROCHIRURGIE(2019)

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摘要
Aim: The aim of the study was to investigate expression changes of pro-inflammatory and proapoptotic cytokine tumor necrosis factor alpha (TNF alpha) and microRNAs (miRNAs) involved in its regulation in early pathophysiological changes after subarachnoid haemorrhage (SAH). Materials and methods: MiRNAs (miR-125b, miR-146a, miR-346, miR-155, miR-15b) and mRNA (TNF alpha) expression were determined by quantitative real-time polymerase chain reaction in brain tissue samples. A total of 88 animals were divided to Sham (control surgery without induction of SAH), Mild SAH, Severe SAH groups in following time-points: 2, 4, 6 and 8 h (n = 7 per group); including 4 animals used as an absolute control. Results: We have found a statistically significant difference in TNF alpha expression between Sham and Severe SAH groups at all the time-points (p < 0.05), between Sham and Mild SAH groups 4 h after induction of SAH (p < 0.05) and between Mild and Severe SAH groups at 2 and 6 h time-points (p < 0.05). Furthermore, a significant difference in miR-15b expression between Sham and Severe SAH groups was observed 8 h after SAH (p < 0.05). All the other microRNAs have not been significantly changed. Conclusions: SAH was associated with an early increase in TNF alpha and miR-15b expression especially in Severe SAH group. Despite complex cross-regulation between cytokines and miRNA, any information about the activation of inflammation/apoptotic mechanisms within a few hours after SAH may improve our knowledge of SAH pathophysiology. Furthermore, it can lead to therapeutic improvement using a combination of both pro-apoptotic markers TNF alpha and miR-15b.
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关键词
subarachnoid haemorrhage,early brain injury,inflammation,apoptosis,microRNA,perforation model
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