Preliminary investigation on the correlation between karyopherin alpha 4 and acute cerebral infarction

Acute cerebral infarction (ACI) has a high incidence and complex etiology, so searching for specific diagnosis and therapeutic target molecules is highly important. This paper aimed to explore the mechanism of karyopherin alpha 4 (KPNA4) in ACI.

Four groups were established: sham group, middle cerebral artery occlusion (MCAO) group, MCAO + small interfering negative control (si-NC group), and MCAO + si-KPNA4 group. The Zea-Longa scoring standard was adopted to assess the neurological impairment of ACI rats. The expression of KPNA4 was verified by real-time quantity polymerase chain reaction assay and Western blot. 2,3,5-Triphenyltetrazolium chloride and hematoxylin and eosin staining were used to examine the effects of KPNA4 knockdown on brain injury in ACI rats. The apoptosis of oxygen-glucose deprivation (OGD)-SH-SY5Y cells was measured by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method. Western blot analysis was performed to analyze the expression levels of apoptosis-related proteins, inflammatory factors, and nuclear factor kappa B (NF-κB) pathway-related proteins.

KPNA4 was overexpressed in the MCAO rat brain (P < 0.0001) and OGD-SH-SY5Y cells (P < 0.0001). Knocking down KPNA4 significantly reduced the degree of brain damage (P < 0.0001) and reduced the apoptosis of OGD-SH-SY5Y cells (P < 0.001). KPNA4 knockdown also significantly decreased the expression levels of inflammatory factors (interleukin [IL]-1β, tumor necrosis factor-α, and IL-18; P < 0.0001) and prohibited the phosphorylation of the inhibitor of NF-κB and p65 (P < 0.0001). However, NF-κB agonist lipopolysaccharide reversed the inhibition of KPNA4 knockdown.

In general, KPNA4 knockdown can mitigate ACI-induced damage by regulating the NF-kB pathway. This finding provides a new perspective on the treatment of ACI.