| [ Background and Purpose ] Cerebral ischemia-reperfusion injury was a complex pathophysiological process, the mechanisms were not well known. At present, oxygen-derived free radical (OFR) injury hypothesis, neurotoxic effects of exciting amino acid (EAA), overloading of intracellular calcium and the role of nitric oxide are prominent. The roles of these factors were not independent, while congenerous. Cerebral ischemic penumbra was firstly proposed by Astrup in 1977 which means neurons remain structural intact but functional inactive, while the function of pumps on cellular membrane and ion gradient were preserved. Recently a new concept of polymolecular penumbra was raised by Sharp. These theories provide novel approaches on study of ischemia or reperfusion injury, mechanisms of recovery and drug intervention.The purpose of drug intervention is to inhibit factors that induce neuron death and restore regional blood flow, then interrupt penumbra progress to necrotic region. At present, many neuroprotective drugs have been developed, including NMDA receptor antagonists, calcium antagonists, free radical scavenger, glucocoiticosteroid, inhibitors of NOS and other anti-inflammatory drugs. But most of them have severe side-effector/and have the poor effects on brain ischemia in clinic. Traditional Chinese medicines especially Bu Yang Huan Wu Decoction have notable effects on cerebral ischemia and have little side-effect. Yiqi Huoxue Decoction is an experience-based prescription which is proposed by Professor Liu Hua, which has chosen to cure ischemic cerebralvascular disease by specialist. It can improve inspiration by invigorating the kidney, activate blood circulation and induce resuscitation.Here we study the effects of Yiqi Huoxue Decoction on neurologic scores, pathologic changes in a transient focal cerebral ischemia/reperfusion model in SD rat. We evaluate inducible nitric oxide synthase (iNOS), constitutive NOS (cNOS), superoxide dismutase (SOD) activities and malondialdehyde (MDA) contents in brain tissue and analyze expressions of NMDA Rlsubunit (NR1), vascular endothelial growth factor(VEGF) and endothelial NOS (eNOS) to determine the protective effect and mechanisms of Yiqi Huoxue Decoction on cerebral ischemia-reperfusion injury in rat and provide evidence to extend the use in clinic.[ Methods ] Focal cerebral ischemia was induced by 60 minutes of middle cerebralartery (MCA) occlusion and followed by 3 days reperfusion. Animals were orally administered with Yiqi Huoxue Decoction (18ml/kg.d-1), nimodipine (Smg/kg.d-1) and vehicle (saline) 1 hour before MCAO and after 4 hours of reperfusion and the following 2 days. The neurological scores were evaluated 4 hours and 3 days after reperfusion. Then the animals were decapitated, brains were stained with 2,3,4,-triphenyltetrazolium chloride (TTC). The infarct volumes, right and left areas of brain section were measured by computer imaging analysis. The Serial coronal sections (10 mm) were obtained by cryoultramicrotomy, the slices were stained with hematoxylin-eosin and toluidine blue, Then the pathologic changes and the normal neurons in hippocampal CA1 and cortex were determined by using an image analyzer. Inducible nitric oxide synthase (iNOS), constitutive NOS (cNOS), superoxide dismutase (SOD) activities and malondialdehyde (MDA) contents in brain tissue were evaluated by spectrophotography. The levels of NMDA Rlsubunit (NR1), vascular endothelial growth factor(VEGF) and endothelial NOS (eNOS) were determined by immunoblotting techniques.[Result] Yiqi Huoxue Decoction and nimodipine improved neuronal dysfunction, reduced infarct size. Yiqi Huoxue Decoction and nimodipine reduced the ratio ofleft/right brain section area, indicating inhibition of brain edema. Yiqi Huoxue Recipe and nimodipine reduced MDA content and iNOS and cNOS activities, increased SOD activity. Western analysis demonstrated induction of NR1 and increase of VEGF, Yiqi Huoxue Decoction has no effect on eNOS.[ Conclusion ] Yiqi Huoxue Decoction has the pro...
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