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

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.