The secondary injury following acute spinal cord injury comprises cell necrosis and apoptosis. Studies have demonstrated that, apoptosis dependent on active protein synthesis contributes to the neuronal and glial cell death, as well as to the neurological dysfunction, induced by mild-to-moderate severity traumatic insults to the rat spinal cord[7]. The key of drug treatment is how to reduce the neural cells apoptosis following acute spinal cord injury and prevent secondary injury.
Li et al[8] firstly reported that there were a great amount expression of neuronal apoptosis related gene and apoptosis protein in rat spinal cord injury models in 1996. bcl-2 is a plasmosin, which was highly expressed in the development of central nervous system and maintained at low level in mature nervous system[9]. It is also thought to be involved in resistance to apoptosis, which can inhibit various apoptosis pathways following spinal cord injury[10]. The mechanism may be related to suppressing free radical production and maintaining membranous structure. Studies demonstrated that, bcl-2 is an inducible gene, the overexpression of bcl-2 can mitigate nerve injury, elevate anti-surgery function of tissues, promote axonal outgrowth and repair of injured central nervous system, as well as inhibit neural cells apoptosis[11-13]. Bax locates in cytoplasm, which precipitates neural cells apoptosis via altering permeability of mitochondrial membrane after activated by receiving information convection of apoptosis[14]. Studiesfound that, the oligodendrocyte apoptosis obvious decreased and the axonal demyelination mitigated when the bax gene was removed after mice spinal cord injury[15]. Scorrano et al[16] found that bcl-2 and bax can alter cell permeability through regulating calcium ion flow. Fan et al[17] demonstrated that bcl-2 and bax expression affect the spinal cord neuronal apoptosis directly or indirectly, and the apoptosis extent is closely associate with its ratio.
Methylprednisolone has received acceptable therapeutic effect in the treatment of spinal cord injury. Tetrandrine can prevent body from acute spinal cord injury by ameliorating microcirculation, inhibiting free radical production, preventing calcium overload, as well as improving tissue metabolism[2-3, 18].
The experiment found that, compared with the sham-surgery group, the expression of bcl-2 and bax were increased after spinal cord injury, which suggested that there were apoptosis. The bcl-2 expression were increased in the methylprednisolone and tetrandrine groups, but bax expression were decreased, the bax expression was highest in the model group, all of these demonstrated that methylprednisolone and tetrandrine play an important role in interfere in expression of apoptotic effector, that is, suppress apoptosis by subliming bcl-2 and depressing bax expression. The expression of bcl-2 and bax reached a peak at 3-7 days after spinal cord injury, and then gradually decreased, which showed that, the apoptosis peaked at 3-7 days, at this time, part of spinal cord function suffered sub-damage still can be retrieved if interfere in time. This was confirmed by the experiment, that the BBB score of the methylprednisolone and tetrandrine groups were greater than the model group at 7 and 14 days. Previous research verified that, hypoxic ischemia, over production of oxygen free radical, as well as peroxidation, lead to membrane permeability increase, calcium overload, and activate endonuclease, finally, induce apoptosis[19]. However, tetrandrine can improve microcirculation, suppress free radical production, and prevent calcium overload[2-3], accordingly, it is supposed to inhibit apoptosis and exhibit protection role in spinal cord injury.
