Protective effects of oleanolic acid on cerebral ischemic damage in vivo and H2O2-induced injury in vitro
Protective effects of oleanolic acid on cerebral ischemic damage in vivo and H2O2-induced injury in vitro
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DOI：
10.3109/13880209.2010.499130
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发表时间：
2011-01-01
影响因子：
3.8
通讯作者：
Ji, Hui
中科院分区：
文献类型：
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作者：
Rong, Zhi-Tao;Gong, Xiao-Jian;Ji, Hui
背景：油酸（OA）是一种三萜类化合物，存在于许多植物中。它具有多种生物活性，在中国已被用于治疗肝炎。目的：首次探讨OA对脑缺血性损伤的保护作用材料与方法：采用双侧颈总动脉结扎（BCCAL）致小鼠脑损伤模型，观察OA对小鼠存活时间的影响。采用大脑中动脉闭塞（MCAO）模型，观察大鼠神经功能、脑梗死面积、脑水肿、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）和丙二醛（MDA）的变化。检测H2 O2损伤后PC 12细胞存活率、乳酸脱氢酶（LDH）、超氧化物歧化酶（SOD）、还原型谷胱甘肽（GSH）、丙二醛（MDA）、线粒体膜电位（MMP）和琥珀酸脱氢酶（SDH）的变化。OA 50和25 mg/kg预给药可显著延长小鼠的存活时间，减轻神经功能、梗死面积和脑水肿，25和12.5mg/kg剂量组大鼠SOD和GSH-Px活性升高，MDA含量降低。用10 μ M和1 μ M的OA预处理显著改善了细胞存活，提高了SOD活性和GSH含量，降低了LDH和MDA水平，并逆转了MMP和SDH活性的降低。这些结果表明，油酸有效地减轻了体内脑缺血损伤和体外氧化损伤，这可能部分是由于内源性抗氧化剂的调节和线粒体功能的改善。油酸可能是一种潜在的抗缺血性脑卒中药物。
Context: Oleanolic acid (OA), a triterpenoid compound, exists in many plants. It has numerous bioactivities and has been used to treat hepatitis in China. However, few studies have reported its effect on the central nervous system, especially in ischemic stroke.Objective: To explore the protective effects of OA on cerebral ischemic injury for the first time.Materials and methods: Survival time was tested in mice injured by bilateral common carotid artery ligation (BCCAL). Neurological function, infarct area, cerebral edema, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were estimated in rats operated by middle cerebral artery occlusion (MCAO). Cell survival, lactate dehydrogenase (LDH), SOD, reduced glutathione (GSH), MDA, mitochondrial membrane potential (MMP) and succinic dehydrogenase (SDH) were detected in H2O2-injured PC12 cells.Results: Pre-administration with OA significantly prolonged survival time in mice at 50 and 25 mg/kg, alleviated neurological function, infarct area and cerebral edema, increased SOD and GSH-Px activities and decreased MDA level in rats at 25 and 12.5 mg/kg. Pre-treatment with OA at 10 and 1 mu M remarkably improved cell survival, enhanced SOD activity and GSH content, reduced LDH and MDA levels and reversed the lowering of MMP and SDH activity.Discussion and conclusion: These results demonstrate that oleanolic acid effectively alleviates cerebral ischemic damage in vivo and oxidative injury in vitro, which may be in part due to the modulation of endogenous antioxidants and the improvement of mitochondrial function. Oleanolic acid may be a potential medicine for attenuating ischemic stroke.