ABSTRACT
Objective:To explore the effect of the enriched environment(EE)on pyroptosis in rats with cerebral ischemia-reperfusion injury(CIRI).Methods:45 male Sprague-Dawley rats were randomly divided into three groups: a sham surgery(Sham)group, a cerebral ischemia-reperfusion(CIR)group and an enriched environment(EE)group, with 15 rats in each group.Except for the Sham group, the right middle cerebral artery occlusion model was established in the other two groups.After surgery, the EE group was fed in EE, and the other two groups were fed in standard environment.All the rats were assessed using the modified neurological severity score(mNSS)before modeling and on the 1st day, 7th day and 14th day following surgery.On the 14th day after surgery, 2, 3, 5-triphenyltetrazolium chloride(TTC)staining was used to evaluate the infarct volume, hematoxylin and eosin(HE)staining was used to examine pathomorphological changes of the hippocampal CA1 region on the ischemic side of the rats in each group, immunohistochemical assay was used to detect the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)and cysteinyl aspartate specific proteinase-1(caspase-1)proteins in the CA1 region, and ultrastructural changes in neurons in the CA1 region were observed under transmission electron microscopy.Results:Compared with the Sham group, the mNSS scores of the CIR group and the EE group were significantly higher on the 1st day and 7th day after surgery( P<0.05), but there was no significant difference between the CIR and EE groups( P>0.05). On the 14th day after surgery, compared with the CIR group, the EE group showed a decrease in the mNSS score and the cerebral infarct volume( P<0.05), alleviated pathomorphological changes, decreased expression of NLRP3 and caspase-1 proteins( P<0.05), and alleviated pathological changes of pyroptosis in the ultrastructure of neurons. Conclusions:EE can reduce the damage of neurological function, reduce the cerebral infarct volume, and play a protective role for the brain in CIRI rats.The mechanism may be related to the down-regulation of the expression of NLRP3 and caspase-1 proteins related to the classical pyroptosis pathway, leading to the inhibition of pyroptosis.
ABSTRACT
Hypoxia-inducible factor-1α (HIF-1α)is a transcription factor that acts as a master regulator of gene expression induced by low oxygen conditions.HIF-1α is the most sensitive indicator of hypoxia and can be activated by systemic hypoxia,cerebral hemisphere ischemia and cerebral focal ischemia.HIF-1 expression can be induced by hypoxic-ischemic damage after cerebral infarction and exert its effects on hypoxia-inducible downstream genes,thus protecting hypoxic tissues and cells under hypoxic conditions via regulating the expression of its downstream target genes.This article reviews the expression of HIF-1α and its downstream target genes in acute cerebral ischemia,in order to provide a theoretical basis for gene therapy.