Protective Effects Of Oxysophoridine On Cerebral Ischemia And Reperfusion Injury In Mice

Objectives To obseve the protective effects of OSR (oxysophoridine, OSR) on cerebralischemia and reperfusion injury in mice and to explore its possible protective mechanismMethods1. To obseve the protective effects of OSR (oxysophoridine, OSR) on cerebralischemia and reperfusion injury in mice①The cerebral ischemic and reperfusion injurymodel of mice was induced with an6/0nylon monofilament coated with silicone hardenermixture via the internal carotid artery.②Neurological deficit scores were teseted with themethod of Bederson、Turgut in mice.③Monopole leads were employed to record thebioelectricity of cerebral frontal cortex. FFT technique was adopted to analyze the cerebralelectrical waves for the total power and the frequency distribution in mice.④The area ofcerebral infarction and the volume of cerebral infarction were assessed with the method of TTCstaining in mice.⑤Brain water content was determined by dry/wet weight method and counted the cerebralindex in mice.2. To explore the possible protective mechanism of OSR on cerebral ischemia andreperfusion injury in mice①Brain tissues were collected to measure the levels ofadenosine-triphosphate(ATP), Maleic Dialdehydle(MDA), glutathione peroxidase (GSH-Px), superoxidedismutase (SOD), catalase(CAT), nitric oxide(NO), nitric oxide synthase(NOS) and lactatedehydrogenase(LDH) with the method of spectrophotometry in mice.②The expression ofNMDA NR1mRNA and the expression of NMDA NR1protein were tested with the methodof Real-time RT-PCR and Western blot in mice.Results1. Protective effects of OSR on cerebral ischemia and reperfusion injury in mice.Compare to the model group, OSR (125,250mg/kg) and nimodipine（6mg/kg）reduced the neurological deficits scores (P<0.01). Compare to the model group, OSR (125,250mg/kg) andnimodipine（6mg/kg）could accelerate the recovery of the δ, θ, α and βwaves. Compare tothe model group, OSR (62.5mg/kg）increased the proportions of δ and θwaves(P<0.05，P<0.01), meanwhile the proportions of α and β waves were decreased(P<0.01),OSR (125,250mg/kg) and nimodipine（6mg/kg）inhibited the decline of total power(P<0.05，P<0.01),enhanced the proportions of δ and θwaves(P<0.01), meanwhile the proportions of α and βwaves were decreased(P<0.05，P<0.01). Compare to the model group, OSR (125,250mg/kg)and nimodipine（6mg/kg）reduced the volume of cerebral infarction (P<0.05，P<0.01). Compareto the model group, OSR (62.5,125,250mg/kg) and nimodipine（6mg/kg）reduced the brainwater content (P<0.01). Compare to the model group, OSR (125,250mg/kg) and nimodipine（6mg/kg）reduced the cerebral index (P<0.05，P<0.01).2. Possible protective mechanism of OSR on cerebral ischemia and reperfusion injury inmice. Compare to the model group,OSR (62.5,125,250mg/kg) and nimodipine（6mg/kg）reduced the contents of MDA、NO(P<0.01) and increased the contents of ATP(P<0.01).Compare to the model group,OSR (62.5,125,250mg/kg) and nimodipin（e6mg/kg）enhancedthe activities of SOD,GSH-PX,LDH and CAT(P<0.01). Compare to the model group,OSR(125,250mg/kg) and nimodipine（6mg/kg）decreased the activity of NOS(P<0.01). Compareto the model group, mRNA and protein expression of NMDA NR1were decreased byOSR(250mg/kg) and nimodipine（6mg/kg）(P<0.01).Conclusions OSR has significant protective effects of cerebral ischemia and reperfusioninjury in mice, the effective mechanism of OSR might relate to the alleviation of oxidativestress and inhibit the expression of NMDA NR1receptor.