Effect of tacrolimus on apoptosis and expression of heat shock protein 70 after acute spinal cord injury in rats

Abstract

To investigate the effect of tacrolimus on expression of heat shock protein 70 (HSP 70) after spinal cord injuries (SCI) in rats and the relationship between expression of HSP 70 and apoptosis of neural cells. Seventy-two male rats were divided randomly into three groups: the sham-operation group, the injury group and the group treated with tacrolimus, and the latter two groups were SCI with a weight-drop impactor at the T(10) vertebrae level (10 g weight was dropped from a 4.0 cm height). The tacrolimus group was injected with tacrolimus 5 minutes after SCI, while the other groups received 0.9% saline likewise. The inclined plate and BBB (Basso, Beattie and Bresnahan) scales were used to evaluate hindlimb neurological function. The expression of HSP 70 mRNA after SCI was detected by using reverse transcription polymerase chain reactions (RT-PCR) and immunohistochemistry staining was performed to determine the protein expression of HSP 70 and Caspase-3. The apoptosis of neural cells was assessed with the terminal deoxynucleotidyl transferase-mediated deoxyuredine triphosphate-digoxin nick end labeling (TUNEL) method. Compared with the injury group, the expression of HSP 70 was significantly higher in the tacrolimus group, and the peak expression of HSP 70 mRNA and protein was respectively observed at 6, 24 h after SCI. Caspase-3-positive or TUNEL-positive cells were significantly less in the tacrolimus group than in the injury group. Neurological function score of the tacrolimus group was significantly better than that of the injury group. Tacrolimus may inhibit activity of Caspase-3, attenuate apoptosis of neural cells and ameliorate neurological function recovery after SCI by inducing high expression of HSP 70.