Can J Physiol Pharmacol . 2018 Jun;96(6):611-617. doi: 10.1139/cjpp-2017-0586. Epub 2018 Mar 5.

本文采用的英格恩产品: RNA-Entranster-invivo

The role of microRNA-146a in regulating the expression of IRAK1 in cerebral ischemia-reperfusion injury

Bo Chu  1   2 Yadong Zhou  3 Heng Zhai  4 Lei Li  5 Li Sun  1 Yun Li  1


  • 1 a Department of Critical Medicine, Jinan Central Hospital of Shandong University, Jinan, Shandong 250013, People’s Republic of China.
  • 2 b Department of Emergency Medicine, Tai’an Central Hospital, Tai’an, Shandong 271000, People’s Republic of China.
  • 3 c Department of Emergency Medicine, Affiliated Hospital of Taishan Medical University, Tai’an, Shandong 271000, People’s Republic of China.
  • 4 d Department of Emergency Medicine, Zibo Central Hospital, Zibo, Shandong 255036, People’s Republic of China.
  • 5 e Department of Critical Medicine, Shandong Chest Hospital (Eastern Branch), Jinan, Shandong 250013, People’s Republic of China.


MicroRNA-146a (miR-146a) is reportedly implicated in the pathogenesis of ischemia-reperfusion (I/R) injury; however, its role in cerebral I/R injury is unclear and requires further investigation. In this study, cerebral I/R injury was established in mice via middle cerebral artery occlusion, and the expression of miR-146a was detected in the brain tissue via quantitative real-time PCR. We found that the expression of miR-146a was upregulated. Furthermore, the endogenous miR-146a was antagonized by its specific inhibitor. The results indicated that the inhibition of miR-146a deteriorated I/R-induced neurobehavioral impairment, exaggerated the infarct size, and exacerbated blood-brain barrier leakage. Cerebral I/R injury-induced generation of inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, was further promoted by miR-146a inhibitor. The expression of interleukin-1 receptor associated kinase 1 (IRAK1), a target of miR-146a, was upregulated upon miR-146a inhibition. In addition, the nuclear factor κB (NF-κB) signaling pathway was over-activated when miR-146a was antagonized as manifested by the increased levels of phospho-NF-κB inhibitor α and nuclear p65. In summary, our findings demonstrate that the elevation of miR-146a may be one of the compensatory responses after the cerebral I/R injury and suggest miR-146a as a potential therapeutic target for cerebral I/R injury.

Keywords: IRAK1; NF-κB; cerebral I/R injury; inflammatory response; lésions d’I/R cérébrales; miR-146a; réaction inflammatoire.