Experimental Research Of Effects Of Pinocembrin On Cerebral Ischemia

Stroke is the general term for cerebral thrombosis and cerebral hemorrhage, a high mortality and high disabling disease. Ischemic stroke and hemorrhagic stroke are two types of stroke, and approximately 80% of stroke results from ischemia.Brain tissue is very sensitive to ischemia, and a short period of ischemia results in irreversible damage of neurons. Since 1995, tPA has been widely used in the treatment of acute ischemic stroke, while tPA would be administered within 3 hours to be effective for the treatment of cerebral ischemia, leading to certain restrictions in application. A large number of experiments are focused on the findings of effective neuroprotective drug that protects living cells in ischemic penumbra. But so far, many drugs in the treatment of cerebral ischemia in PhaseⅢclinical trials have not yet achieved success.Pinocembrin was found for the treatment of cerebral ischemia in our laboratory by high throughput screening modes of Na+/H+ exchanger, intracellular calcium screening model and resazurn model of nerve cell activity. Previous studies find that pinocembrin has a variety of pharmacological activities, including antibacterium, antivirus, antioxidation, anti-inflammation, antitumor, anti-obesity.To investigate the effects of pinocembrin on cerebral ischemia, the present study used bilateral common carotid artery ligation, electrocoagulation bilateral vertebral artery model of global cerebral ischemia (4-VO) in rats. We also cultured brain microvascular endothelial cells and astrocytes cells in vitro, and research the effects of pinocembrin on brain microvascular endothelial cells injury induced by oxygen-glucose deprivation/reperfusion, as well as the effects of pincombrin on astrocytes injury caused by hydrogen peroxide.The present study found that pinocembrin protected blood brain barrier against the injury induced by global cerebral ischemia/reperfusion reduced the blood-brain barrier permeability. Pinocembrin reduced edema of astrocyte feet, alleviated microvascular occlusion compressed by swelling astrocyte feet. Pinocembrin improved cerebral blood flow of global cerebral ischemia rats, and had no significant effects on cerebral blood flow in the normal rats. The effects of pinocembrin on cerebral blood flow may be related to diastolic function and protection of the brain microvascular endothelial cells.Pinocembrin reduced the inflammation of brain tissue in global cerebral ischemia and reperfusion rats. Pinocembrin reduced MPO activity, brain tissue NO levels and iNOS activity, and reduced levels of TNFαand IL-1β.Pinocembrin alleviated the injury of primary cultured brain microvascular endothelial cell induced by oxygen-glucose deprivation/reperfustion. Pinocembrin increased endothelial cell survival, ATP generation, and mitochondrial membrane potential. Pinocembrin also reduced the injury of primary cultured astrocyte induced by H2O2. Pinocembrin increased the survival rate of astrocytes, ATP level, and mitochondrial membrane potential. And pinocembrin alleviated the apoptosis of astrocyte.In summary, pinocembrin protected brain tissue against cerebral ischemia, reduced blood-brain barrier damage and neuronal death, and improved learning and memory. Pinocembrin reduced the inflammation of global cerebral ischemia and reperfusion, and lessened neuronal damage. Pinocembrin reduced microvascular endothelial cell damage against oxygen-glucose deprivation/reperfusion, and reduced oxidative damage of astrocyte caused by hydrogen peroxide. Pinocembrin also improved cerebral microcirculation in 4-VO rats, and increased brain function reservation. Therefore, pinocembrin may protect microvessels, neurons and astrocyte against the damage induced by global cerebral ischemia/reperfusion, and pinocembrin may protect global cerebral ischemia-reperfusion rats through a variety of mechanisms.