Plasmid PLXSN-mediated Transfer Of The Human Bcl-2 CDNA Inhibits Apoptosis Of Neural Cells During Focal Cerebral Ischemia In Rat Brain

PrefaceApoptosis appears to contribute to postischemic neuronal death in stroke and the expression of the bcl - 2 gene has been shown to rescue neuronal cells from programmed cell death. Plasmid pLXSN was used to transduce human bcl - 2 cDNA in present study to observe the neu-roprotection of plasmid pLXSN - mediated transfer of bcl - 2 gene during focal cerebral ischemia.Methods54 male Wistar rats were randomly divided into three groups; normal saline ( NS ) control group, plasmid control group, bcl - 2 group. NS , plasmid - pLXSN and plasmid - pLXSN - bcl - 2 were respectively injected into two sites in the rat right cerebral cortex 24 hours before induction of neocortical focal ischemia by occlusion of the right middle cerebral artery for 24 hours. The condition of local ische-mic damage, expression of bcl - 2 and the apoptosis in neural cells were confirmed respectively by staining with 2% 2,3,5 -triphenyltet-razolium chloride, immunohistochemistry, in site cell apoptosis detection and flow cytometry.ResultsIn the injection sites 1, 2 and midpoint, the extent of viable tissue from the longitudinal fissure to the medial edge of the infarction were measured with a surveyor's rod. It was respectively (2.70 ±0. 36)mm,(2.52±0.27)mm,(2.33 ±0. 16)mm in NS control group; (2. 83 ±0.47)mm,(2. 59 ±0. 67) mm,(2. 63 ±0. 38)mm in plas-mid control group and' (4.22 ±0. 80) mm, (4. 77 ±0.74) mm, (3. 57 ± 1.49) mm in bcl -2 group. In the injection sites viable tissue of bcl - 2 group were significantly increased ( P < 0.01). The expression of bcl -2 in bcl -2 group (1.9517% ±0.6522% ) than those in NS control group (0. 9306% ±0. 2611% ) or in plasmid control group (0.9527% ±0. 3674% ) was significantly increased( P <0. 01). The apoptosis in neural cells in bcl -2 group (38. 35 ±3. 02) than those in the NS control group (61. 67 ± 13. 55) or in the plsmid control group (58. 33 ± 15. 25) was significantly reduced (P <0.01 or P <0. 05).Discussionlnthe injection sites viable tissue, the expression of bcl - 2 and the apoptosis in neural cells in bcl - 2 group were all significantly change than those in NS control group or in plasmid control group. It indicates that plasmid pLXSN - mediated transfer of bcl - 2 gene may rescue neuronal cells by inhibiting apoptosis of cells in stroke. The results in NS control group or in plasmid control group were not significantly different, which showed the effect and safe of the plasmid pLXSN.ConclusionPlasmid pLXSN - mediated transfer of bcl - 2 gene may inhibit apoptosis of neurol cells to result in neuroprotection during focal cerebral ischemia.