Protective Effects Of Oleanolic Acid On Cerebral Ischemia/Reperfusion Injury In Mice

Objective To study the protective effect of oleanolic acid on cerebral ischemia reperfusion injury and its protective mechanism.Methods The model of cerebral ischemia reperfusion injury in mice was established by middle cerebral artery occlusion(MCAO).Both the short-term effect(-24h after injury)and long-term effect(9 weeks following injury)of oleanolic acid on cerebral ischemiareperfusion injury were observed respectively after 3 days of administration before model establishment or 6 weeks after model establishment(intraperitoneal injection,6 mg/kg/d).Indicators of short-term effects include measurement of cerebral infarction area by TTC staining,blood-brain barrier permeability(Evans blue leak experiment and Western Blot analysis of tight junction protein expression level),and oxidative stress level(DHE staining and MDA quantitative analysis).Long-term performance indicators include dynamic changes in neurological symptom scores,motor function measured by rota-rod method,and behavioral experiments(open field experiments and new object recognition).The brain tissue loss area was calculated by Nissl staining;The activation of glial cells in the hippocampus and the number of DCX positive cells were observed by immunofluorescence;The expression levels of GFAP,Ibal and synapse-related proteins PSD95,Synapsin and Synaptophysin in the hippocampus were quantitatively analyzed by Western Blot.Results 1.Preventive administration of oleanolic acid could significantly reduce the cerebral infarction area and neurological symptom score 24 hours after ischemiareperfusion injury,inhibit the expression of Evans blue leakage and Occludin,and reduce DHE fluorescence staining and MDA levels.2.The treatment with oleanolic acid could significantly reduce brain loss and enhance the motor function,promote the recovery of nerve function,and improve the learning and memory ability after 9 weeks of ischemia-reperfusion injury.Oleanolic acid could also inhibit the proliferation of astrocytes and the activation of microglia,promote the expression of synapse-related proteins and increase the number of DCX+cells in the hippocampus.Conclusions Oleanolic acid has both short-term and long-term protective effects on cerebral ischemia-reperfusion injury in mice.The short-term protective mechanism is related to the antioxidant protection of blood-brain barrier,while the long-term protective mechanism is related to the inhibition of inflammation in the brain and the promotion of synaptic connection and nerve regeneration...