Effects Of Propofol On The Neuronal Apoptosis And Its Mechanisms After Acute Spinal Cord Injury In Rats

The acute spinal cord injury can be divided into two stages, the primary injury and the secondary injury. The primary injury, which caused by the outer force, is irreversible, thus, it is impossible to treat it in time. On the other hand, the secondary injury is progressive, which is caused by different factors and induces more sever injury than the primary injury, we should pay more concern on this stage and provide medicinal treatment.Recently, with the rapid progress of the study on spinal cord injury, many theories have been founded and some of them, such as the oxygen-derived free radicals, calcium overload and excitive amino acid theory, have been accepted by many researchers. Apoptosis occurred in the spinal cord injury has also been found playing an important role during the secondary injury. The apoptosis is referred to an active death procedure mediated by genes on some kinds of physical and pathological state. Since the apoptosis is a programmed death procedure , it is possible for us to mediate the procedure. Thus it has become the focus field of spinal cord injury researches. It still has not been reported about the effects of clinical anesthetic on the apoptosis after spinal cord injury up to now. Therefore, To study the effects of clinical anesthetic and their mechanism has great important significance for the clinical medical treatment to relieve the secondary injury and achieve a better recover.By using TUNEI PI /Heochst33342, immunohistochemistry and so on, we studied the effect of propofol on apoptosis of the primary cultured spinal cord neuron and the rat neuronal cell after acute spinal cord injury, and the expression of related genes were also observed. Our data suggested that propofol could mediate the expression of gene bax and bcl-2, inhibit the apoptosis, relieve secondary injury, and protect the spinal cord function. The main results:Our observations on the primary cultured spinal cord neuron indicated that the 7th day is the best time for us to observe their morphologic state and test their activities. This result provided good references for related researches.TNF- could inhibit the expression of bcl-2 and enhance the expression of bax in primary cultured spinal cord neurons, which result in the increase of bax/bcl-2 and the apoptosis of the primary cultured spinal cord neurons.Propofol could enhance the expression of bcl-2 and inhibit the expression of bax in primary cultured spinal cord neurons, and the decrease of bax/bcl-2 caused finally induced the inhibition of apoptosis and this effect is dose dependent.The analysis of MDA levels and SOD activities in the serum of rat after spinal cord injuries showed the important role of peroxygenation of lipid caused by oxygen-derived free radicals in the secondary injuries, and Propofol could protect the spinal cord from the harm of lipid oxygenation.The using of inclined plane test and BBB locomotor rating scale indicated that Propofol 60mg kg-1 h-1, 30mins after spinal cord injury, could enhance the behavior functional recovery of rat. BBB locomotor rating scale is more objective and exact compared with the inclined plane test.The detection after injury with TUNEL provided the further evidences of the existence of apoptosis in spinal cord injuries and the inhibitory effect of Propofol on apoptosis.