Effect of transgenic human insulin-like growth factor-1 on spinal motor neurons following peripheral nerve injury

摘要

The aim of the present study was to observe the protective effect of exogenous human insulin-like growth factor-1 (hIGF-1) on spinal motor neurons, following its local transfection into an area of peripheral nerve injury. A total of 90 male Wistar rats that had been established as sciatic nerve crush injury models were randomly divided into three groups: hIGF-1 treatment, sham-transfected control and blank control groups. The different phases of hIGF-1 expression were observed in the spinal cord via postoperative immunostaining and the apoptosis of motor neurons was observed using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method. Pathological changes of the motor neurons and Nissl bodies within cell bodies were observed via Marsland and Luxol fast blue double staining, while changes in the neuropil of the spinal cord anterior horn were investigated via ultrastructural observation. It was found that hIGF-1, locally transfected into an area of peripheral nerve injury, was expressed in the spinal anterior horn following axoplasmic transport; the peak hIGF-1 expression occurred approximately a week following transfection. The number of apoptotic spinal cord motor neurons observed in the hIGF-1 treatment group was fewer than that in the sham-transfected and blank control groups at days 7, 14 and 21 following transfection (P<0.01). Furthermore, the quantity of motor neuron cells in the anterior horn of the spinal cord in the hIGF-1 treatment group was higher compared with those in the sham-transfected and blank control groups at days 2, 7, 14 and 28 following transfection (P<0.01). The degenerative changes of Nissl bodies within the cytoplasm of the hIGF-1 treatment group were less severe compared with those of the sham-transfected and blank control groups. At day 56 following transfection, the spinal anterior horn neuropil ultrastructure in the hIGF-1 treatment group was generally normal, while the sham-transfected and blank control groups exhibited an increased number of protruding gaps and local cavities. These results indicate that the application of exogenous hIGF-1 is capable of protecting spinal cord motor neurons following peripheral nerve injury.