Nicorandil Inhibits Inflammasome Activation and Toll-Like Receptor-4 Signal Transduction to Protect against Oxygen-Glucose Deprivation-Induced Inflammation in BV-2 Cells

作者：Zhao, An-Peng; Dong, Yin-Feng; Liu, Wei; Gu, Jun; Sun, Xiu-Lan^*

来源：CNS Neuroscience & Therapeutics, 2014, 20(2): 147-153.

DOI：10.1111/cns.12178

• ATP-sensitive potassium channel
• Inflammasome
• Neuroinflammation
• Nicorandil
• Oxygen-glucose deprivation

Background and purposeOur previous studies have demonstrated adenosine triphosphate-sensitive potassium channel (K-ATP channel) openers could protect against inflammatory response in brain disease, but little is known about the mechanisms involved in K-ATP channel openers inhibiting neuroinflammation.
Methods and resultsIn the present study, we found that oxygen-glucose deprivation (OGD) resulted in BV-2 cells activation, significantly increased tumor necrosis factor-alpha and interleukin-1beta (IL-1) levels, accompanied by downregulating Kir6.1 subunit. Pretreatment with nicorandil, a K-ATP channel opener, could attenuate OGD-induced BV-2 cells activation and inhibit pro-inflammatory factors release. Further study demonstrated that OGD activated Toll-like receptor-4 (TLR4) signaling pathway and NOD-like receptor pyrin domain containing three inflammasome, thereby increased IL-1 production. Pretreatment with nicorandil could reverse the two pathways involved in IL-1 production.
ConclusionsOur findings reveal that K-ATP channel openers could protect against OGD-induced neuroinflammation via inhibiting inflammasome activation and TLR4 signal transduction.

• 出版日期2014-2
• 单位南京中医药大学; 南京医科大学