Effects Of Dextromethorphan On Neuronal Injury And Expression Of Bcl-2 Induced By Focal Ischemia-Reperfusion In Rats

Objective: To investigate the effects of preconditioning with dextromethorphan on neuronal apoptosis induced by focal cerebral ischemia-reperfusion injury in rats and possible mechanisms, after establishing the animal model of reversible middle cerebral occlusion(MCAO).Methods: MCAO model was produced with intraluminal suture technique reference to Magasawa and ZeaLonga's method. Male S-D rats (n=40, weighing 250~300g) were randomly allocated to 5 groups. SHAM group: sham operation group(n=5); I/R group: ischemia-reperfusion group(n=5), intraperitoneal injected with saline 3ml; DM10 group(n=10), DM30 group(n=10), DM50 group(n=10), intraperitoneal injected with dextromethorphan 10mg/kg, 30mg/kg, 50mg/kg respectively 30min before MCAO. At 2h and 24h after reperfusion, the extent of neurological deficits were evaluated by modified Neurological Severity Scores (mNSS) . Morphological changes of brain were observed. Brain cell apoptosis were tested by TUNEL methods. Bcl-2 mRNA expression were assessed with RT-PCR methods.Results: 1. In I/R group, versus SHAM group, the neurological syndromes and injury change of brain histology were showed, apoptotic cells increased and apoptotic index(AI) elevated(P<0.01), the expression of Bcl-2 mRNA were higher(P<0.01). 2. The three DM groups comparing with SHAM group were similar to I/R group. 3. In DM groups ,comparing with I/R group ,the neurological function improved significantly, the brain histology improved significantly, the apoptotic index decreased while the expression of Bcl-2 mRNA were higher(P<0.05). 4. The effects on ischemia-reperfusion injury differed among the three DM group. In DM30 group and DM50 group, as for DM10 group, the effects of preconditioning were more prominent comparatively.Conclusions: MCAO model produced with intraluminal suture techinique simulate...