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目的:研究熊果酸对大鼠局灶性脑缺血再灌注损伤的保护作用并探讨其作用机制。方法:120只清洁级雄性SD大鼠随机分为假手术组、局灶性脑缺血再灌注模型组、熊果酸(20,40,80,120 mg·kg-1)治疗组,每组20只。采用颈内动脉线栓法制备大鼠局灶性脑缺血再灌注模型,术后通过尾静脉注射给药。6 h后,盲法行神经功能评分,测定脑梗死体积及脑组织含水量,测定血清中肌酸激酶(CK),乳酸脱氢酶(LDH),丙二醛(MDA)含量以及总抗氧化能力(T-AOC);检测脑组织中超氧化物歧化酶(SOD),谷胱甘肽过氧化物酶(GSH-Px),过氧化氢酶(CAT)活性及MDA含量;通过苏木精-伊红(HE)染色法观察脑组织病理形态学改变。结果:与假手术组比较,局灶性脑缺血再灌注模型组大鼠出现明显的行为障碍,血清中CK,LDH,MDA含量显著降低(P<0.01),T-AOC显著降低(P<0.01),脑梗死体积和脑组织含水量显著升高(P<0.01),脑组织中SOD,GSH-Px,CAT活性显著升高(P<0.01),并且脑组织出现明显的病理性改变;与脑缺血再灌注模型组相比,熊果酸(40~120 mg·kg-1)治疗组大鼠行为障碍显著好转(P<0.05,P<0.01),血清中CK,LDH,MDA含量显著降低(P<0.05),T-AOC显著升高(P<0.05,P<0.01);熊果酸(80,120 mg·kg-1)治疗组脑梗死体积和脑组织含水量显著降低(P<0.05,P<0.01),脑组织中SOD,GSH-Px,CAT活性显著升高(P<0.05,P<0.01),MDA含量显著降低(P<0.05);脑组织病理形态学改变明显减轻,其中以熊果酸120 mg·kg-1治疗组效果最为显著。结论:熊果酸对大鼠脑缺血再灌注损伤具有剂量依赖性的保护作用,该作用可能与熊果酸有效改善抗氧化酶系统活性、减轻自由基损伤有关。
Objective: To study the protective effect of ursolic acid on focal cerebral ischemia-reperfusion injury in rats and its mechanism. Methods: Totally 120 male SD rats were randomly divided into sham-operation group, focal cerebral ischemia / reperfusion model group and ursolic acid (20, 40, 80 and 120 mg · kg-1) . The model of focal cerebral ischemia-reperfusion in rats was made by the method of internal carotid artery occlusion. After the injection, the rats were injected through tail vein. Six hours later, the neurological function score, the volume of cerebral infarction and the water content of brain tissue were measured by blind method. The levels of serum creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA) and total antioxidant (T-AOC). The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) Eosin (HE) staining was used to observe the histopathological changes of brain tissue. Results: Compared with the sham operation group, the rats in the Focal Cerebral Ischemia / Reperfusion Model had obvious behavioral disorders. The levels of serum CK, LDH and MDA were significantly decreased (P <0.01) and T-AOC was significantly decreased (P < 0.01). The volume of cerebral infarction and water content in brain tissue were significantly increased (P <0.01). The activity of SOD, GSH-Px and CAT in brain tissue were significantly increased (P <0.01), and the pathological changes of brain tissue were observed. Compared with the model group, the behavioral deficit in the ursolic acid (40-120 mg · kg -1) group was significantly improved (P <0.05, P <0.01), the content of CK, LDH and MDA (P <0.05, P <0.01). The volume of cerebral infarction and the water content of brain tissue in the treated group of UA (80,120 mg · kg-1) were significantly decreased (P < 0.05, P <0.01). The activities of SOD, GSH-Px and CAT in brain tissue were significantly increased (P <0.05, P <0.01) Among them, ursolic acid 120 mg · kg-1 treatment group was the most effective. CONCLUSION: Ursolic acid has a dose-dependent protective effect on cerebral ischemia-reperfusion injury in rats. This effect may be related to the fact that ursolic acid can effectively improve antioxidant system activity and reduce free radical damage.