Protective Effects Of Total Flavones Of Rhododendra Against Cerebral Ischemia Reperfusion Injury

Objective To study the protective effects and possible mechanisms of total flavones of rhododendra(TFR) against cerebral ischemia reperfusion injuryMethods(1) TFR was administrated by gavage once a day for 5 days.Focal cerebral ischemia/reperfusion injury was caused by occluding the right middle cerebral artery(MCAO).The numerical data,which were from infarct volume, neurological deficit,brain water content,level of malondialdehyde(MDA) and nitric oxide(NO),lactate dehydrogenase(LDH) and superoxide dismutase(SOD) activities in plasma were evaluated.(2) Global cerebral ischemia/reperfusion injury was caused by four vessel occlusion(bilateral vertebral arteries and bilateral carotid arteries, 4-VO).The electroencephalographic(EEG) changes were recorded.The EEG,brain water content,levels of MDA content and LDH activity in plasma were measured.HE staining was used to observe brain pathologic changes.(3) Aggregation of platelets induced by ADP was examined(4) The resting and CaCl₂-induced increase of intracellular free calcium concentration([Ca²⁺]_i),was evaluated.(5) The effect of TFR on the percentage of cerebral blood flow,blood pressure,heart rate and electrocardiographic were detected in dog.Results(1) TFR(50.0,25.0,12.5,6.25 mg/kg) dramatically decreased infarct volume, ameliorated the neurological deficit and reduced the brain water content.The activity of SOD in plasma were enhanced,while the activity of LDH in plasma and the contents of MDA and NO in plasma were reduced by TFR(50.0,25.0,12.5 mg/kg). (2) TFR(25.0,12.5,6.25 mg/kg) significantly elevated EEG amplitude,improved brain pathologic changes,reduced the brain water content and decreased the LDH activity and the MDA content in plasma.(3) TFR(25.0,12.5,6.25 mg/kg) had an inhibitory effect on platelet aggregation.(4) TFR(25.0,12.5,6.25 mg/kg) reduced the resting[Ca²⁺]_i and TFR(25.0,12.5 mg/kg) inhibited the increase of[Ca²⁺]_i induced by CaCl₂.(5) TFR(40 mg/kg) increased the cerebral blood flow in anaesthesia dog.Conclusion These results indicate that TFR has protective effects against cerebral injury in rats,which might be associated with its antioxidant properties,antiplatelet effects and reducing of[Ca²⁺]_i.