目的:研究熊果酸对大鼠永久性局灶性脑缺血损伤的保护作用并探讨其作用机制。方法:140只SPF级雄性SD大鼠随机分为假手术组、脑缺血模型对照组、熊果酸(20、40、80和120 mg/kg)治疗组、舒血宁注射液(0.9 m L/kg)阳性对照组,每组20只。采用颈内动脉线栓法制备大鼠大脑中动脉阻塞(p MCAO)模型,插入栓线后立即尾静脉注射给药。术后6 h行盲法神经功能缺失评分,测定脑梗死体积(IV%)和脑组织含水量,采用荧光标记法测定神经细胞胞浆Ca2+浓度[Ca2+]i,并通过苏木精-尹红(HE)染色观察脑组织病理形态学改变。结果:与脑缺血模型对照组相比,熊果酸(40、80和120 mg/kg)治疗组大鼠神经功能评分显著降低(P<0.05,P<0.01)、胞浆[Ca2+]i浓度显著降低(P<0.05,P<0.01),熊果酸(80和120 mg/kg)治疗组脑梗死体积和脑组织含水量均显著降低,脑组织病理形态学改变明显减轻。结论:熊果酸对大鼠永久性局灶性脑缺血损伤具有保护作用,该作用可能与其抑制Ca2+内流有关。 Objective: To study the protective effect of ursolic acid on permanent focal cerebral ischemic injury in rats and its mechanism. Methods: One hundred and forty SPF male Sprague-Dawley rats were randomly divided into three groups: sham operation group, cerebral ischemia model control group, ursolic acid (20, 40, 80 and 120 mg / kg) L / kg) positive control group, 20 in each group. The model of middle cerebral artery occlusion (MCAO) in rats was established by the method of internal carotid artery occlusion. Immediately after insertion of the plug, the tail vein was used for injection. Six hours after operation, the neurological deficit score of blindness was measured, the volume of cerebral infarction (IV%) and the water content of brain tissue were measured. The Ca2 + concentration [Ca2 +] i in cytoplasm of nerve cells was measured by fluorescent labeling method and detected by hematoxylin- (HE) staining to observe the histopathological changes of brain tissue. Results: Compared with the cerebral ischemia model group, the neurological scores of the rats treated with ursolic acid (40, 80 and 120 mg / kg) were significantly decreased (P <0.05, P <0.01) (P <0.05, P <0.01). The volume of cerebral infarction and the water content of brain tissue in the treated groups of ursolic acid (80 and 120 mg / kg) were significantly decreased, and the pathological changes of the brain tissue were significantly reduced. Conclusion: Ursolic acid has a protective effect on permanent focal cerebral ischemic injury in rats, which may be related to its inhibition of Ca2 + influx.