【罂粟摘要】右美托咪定通过microRNA-214/ ROCK1/ NF-κB通路实现对脑缺血/再灌注损伤的保护作用
右美托咪定通过microRNA-214/ ROCK1/ NF-κB通路实现对脑缺血/再灌注损伤的保护作用
贵州医科大学 高鸿教授课题组
翻译：张中伟 编辑：佟睿 审校：曹莹
脑缺血/再灌注损伤（CIRI）是外科手术的并发症，死亡率高。以往的研究已经探讨了右美托咪定（DEX）对CIRI的保护作用，但其潜在的分子机制尚不清楚。本研究探讨了右美托咪啶对CIRI的保护作用及其作用机制。
采用大脑中动脉闭塞法（MCAO）建立CIRI大鼠模型。测量MCAO模型和接受DEX治疗的大鼠的神经功能缺损评分。TTC染色法检测大鼠脑梗死面积，HE染色法检测大鼠海马区神经元受损程度。TUNEL染色法检测海马区神经元凋亡率。采用双荧光素酶法检测microRNA-214（miR-214）与Rho相关激酶1（ROCK1）的结合。
DEX可显著减少MCAO大鼠的脑梗死面积，并提高miR-214的表达。miR-214抑制剂通过增加大鼠脑梗死面积和海马神经元凋亡率，从而减轻DEX对MCAO大鼠的影响。miR-214可靶向负性调控ROCK1。ROCK1的过度表达导致NF-κB的激活，从而加重CIRI。
结论
DEX对CIRI的治疗作用是通过miR-214的过度表达，减少ROCK1的表达和NF-κB的活化实现的。我们的发现可能为DEX对CIRI大鼠的治疗机制提供新的见解。
Wenyi Liu, Cuihua Shao, Chuanshan Zang，et al. Protective effects of dexmedetomidine on cerebral ischemia/reperfusion injury via the microRNA-214/ROCK1/NF-κB axis.[J]. BMC Anesthesiol (2021) 21:203: 1.
Protective effects of dexmedetomidine on
cerebral ischemia/reperfusion injury via the
microRNA-214/ROCK1/NF-κB axis
Abstract
Background: Cerebral ischemia/reperfusion injury (CIRI) is a complication of surgical procedure associated with high mortality. The protective effect of dexmedetomidine (DEX) on CIRI has been explored in previous works, yet the underlying molecular mechanism remains unclear. Our study explored the protective effect of DEX and its regulatory mechanism on CIRI.
Methods: A CIRI rat model was established using middle cerebral artery occlusion (MCAO). Neurological deficit scores for rats received MCAO modeling or DEX treatment were measured. Cerebral infarction area of rats was detected by TTC staining, while damage of neurons in hippocampal regions of rats was determined by
hematoxylin-eosin (HE) staining. Apoptosis rate of neurons in hippocampal regions was examined by TUNEL staining. The dual-luciferase assay was performed to detect the binding of microRNA-214 (miR-214) to Rho-associated kinase 1 (ROCK1).
Results: DEX treatment significantly reduced infarction area of MCAO rats and elevated miR-214 expression.Injection of miR-214 inhibitor attenuated the effect of DEX in MCAO rats by increasing the area of cerebral infarction in rats and apoptosis rate of hippocampal neurons. ROCK1 was targeted and negatively regulated by miR-214. The overexpression of ROCK1 led to activation of NF-κB to aggravate CIRI.
Conclusion: Therapeutic effects of DEX on CIRI was elicited by overexpressing miR-214 and impairing ROCK1 expression and NF-κB activation. Our finding might provide novel insights into the molecular mechanism of DEX in rats with CIRI.