Neuroprotective Effect Of Butylphthalide On Cerebral Ischemia-reperfusion Injury

Objective:With the advances of modern medicine and the development of an aging population gradually increased, cerebrovascular accident has become one of the three diseases risk to human health. Among which cerebral ischemia had been gained increasing attention because of high morbidity, high mortality, high morbidity and thus to explore effective drug therapy had became a hot topic of modern medical research.Recent years, with the development of thrombolytic and endovascular treatment for acute cerebral infarction, restoring cerebral ischemic reperfusion is the main treatment, but sometimes it can induce brain damage.Butylphthalide is a kind of levorotatory form extracted from celery seed and then artificial synthesize racemicform. The researches of Institute of Pharmacology of Chinese Academy of Medical Sciences confirmed that butylphthalide can prevent animal's damage from acute ischemic stroke with a variety of mechanisms, but the mechanism for cerebral ischemic reperfusion injury is seldom reported. Our experiment will provide theoretical basis for butylphthalide in mechanisms and clinical indications.Methods:38 male SD rats were randomly divided into sham-operation group (8), medicine control group (15) and butylphthalide group (15). The preparation for ischemia-reperfusion model was blocked middle cerebral artery (Middle Cerebral Artery Occlusion, MCAO) for 2 hours and then lifting block. Sham group animals will be sent to the internal carotid artery suture and pull out after 15mm. In butylphthalide group, the rats were feed butylphthalide (40mg/kg) after 1 h of reperfusion and executed in the third day. The infarct volume and the morphology of infarction area were measured by TTC and HE staining; transmission electron microscopy was used to observed the ultrastructural changes of brain infarction; in situ end labeling (TUNEL) method was used to determine the number of apoptotic cells; and neuron-specific enolase concentrations in serum. was measured by enzyme-linked immuno-sorbent assay (ELISA).Results:The area and volume of cerebral infarction in rats treated with butylphthalide were decreased in comparation with control groups (P<0.05). HE staining showed that butylphthalide could significantly reduce cellular edema, and karyopyknosis of the brain induced by ischemic reperfusion. The ultrastructural morphological changes were ameliorated in the brain of rat treated with butylphthalide, compared to the control group. In butylphthalide treated group, TUNEL-positive apoptotic cells in the cerebral cortex were significant less than that of control group (p<0.05); The concentration of serum NSE in butylphthalide treated group was significantly lower than of the control group(p<0.05).Conclusion:1. Butylphthalide exerted a significant protective effect on reducing neuron-specific enolase concentrations in serum, the number of cells.2. Butyl-phthalide could reduce concentrations of neuron-specific enolase in serum which can be used as an indicators for brain protection.