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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Pan
Feng
F
Department of Orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. panmountains@126.com
Chen
An-min
AM
Guo
Feng-jin
FJ
Zhu
Cheng-liang
CL
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D016559:Tacrolimus / Q000494:pharmacology*
D018840:HSP70 Heat-Shock Proteins; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D053148:Caspase 3; D016559:Tacrolimus