Effects of thymosin β4 on neuronal apoptosis in a rat model of cerebral ischemia‑reperfusion injury.

Abstract

The aim of the present study was to investigate the protective effects of thymosin β4 (Tβ4) on neuronal apoptosis in rat middle cerebral artery occlusion ischemia/reperfusion (MCAO I/R) injury, and determine the mechanisms involved in this process. Forty-eight adult male Sprague-Dawley rats were randomly divided into three groups (n=16 per group): A sham control group, an ischemia/reperfusion group (I/R group), and a Tβ4 group. The focal cerebral I/R model was established by blocking the right MCA for 2 h, followed by reperfusion for 24 h. The Zea-Longa method was used to assess neurological deficits. Cerebral infarct volume was assessed using 2,3,5-triphenyltetrazolium chloride staining, and pathological changes were observed via hematoxylin and eosin staining. The terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay was used to detect apoptosis. The expression of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and caspase-12 (CASP12) protein was assessed using immunohistochemistry and western blotting 24 h after reperfusion. Infarct volume and neuronal damage in the I/R and Tβ4 groups were significantly greater than those observed in the sham group. The Zea-Longa score, neuronal apoptosis, and expression of GRP78, CHOP, and CASP12 in the I/R and Tβ4 groups were significantly higher than those reported in the sham group. However, the Longa score and neuronal apoptosis were lower in the Tβ4 group compared to the I/R group. The expression of GRP78 was significantly increased, whereas that of CHOP and CASP12 was significantly decreased in the Tβ4 group compared to the I/R group. The present data revealed that Tβ4 can inhibit neuronal apoptosis by upregulating GRP78 and downregulating CHOP and CASP12, thereby reducing cerebral I/R injury.