Kaempferol Mediated AMPK/mTOR Signal Pathway Has a Protective Effect on Cerebral Ischemic-Reperfusion Injury in Rats by Inducing Autophagy

Neurochem Res. 2022 Aug;47(8):2187-2197. doi: 10.1007/s11064-022-03604-1. Epub 2022 May 7.

Abstract

Ischemia/reperfusion (I/R) caused by ischemic stroke treatments leads to brain injury and its pathological mechanism is related to autophagy. The underlying mechanism of kaempferol on cerebral I/R injury needs to be explored. To establish I/R injury, we used a middle cerebral artery occlusion-reperfusion (MCAO) model in rats. MCAO rats were treated with the same amount of saline (I/R group); Treatment group rats were treated orally with kaempferol (50, 100, 200 mg/kg) for 7 days before surgery. After reperfusion for 24 h, the scores of neurological deficits and infarct volume in each group were evaluated. LC3, Beclin-1 p62, AMPK and mTOR protein expression levels were examined by TTC staining, immunofluorescence staining, qRT-PCR and western blotting assay. H&E and TTC staining showed that compared with model group, the infarction size of rats in kaempferol group was markedly reduced. Meanwhile, the results showed that kaempferol had a dose-dependent nerve function repairability. Nissl and TUNEL staining showed that kaempferol could reduce neuronal apoptosis and ameliorate neuronal impairment after I/R. Western blotting and qRT-PCR results showed that kaempferol could protect the brain from ischemia reperfusion by activating autophagy. In addition, add AMPK inhibitor, western blotting and immumohistochemical staining showed that kaempferol mediated AMPK/mTOR signal pathway in MCAO rats. Kaempferol could mediate the AMPK signal pathway to regulate autophagy and inhibit apoptosis to protect brain against I/R injury.

Keywords: Apoptosis; Autophagy; Kaempferol; Middle cerebral artery occlusion (MCAO).

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Autophagy
  • Brain Ischemia* / drug therapy
  • Brain Ischemia* / metabolism
  • Brain Ischemia* / prevention & control
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / metabolism
  • Kaempferols / pharmacology
  • Kaempferols / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury* / drug therapy
  • Reperfusion Injury* / metabolism
  • Reperfusion Injury* / prevention & control
  • Signal Transduction / physiology
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Kaempferols
  • mTOR protein, rat
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases