摘要
目的研究20(S)-人参皂苷Rg3对脑缺血所致大鼠脑线粒体损伤的保护作用,探讨20(S)-人参皂苷Rg3抗缺血性脑中风的机制。方法用栓线法制作大鼠大脑中动脉缺血(MCAO)模型,测定线粒体肿胀度、膜流动性、膜磷脂含量、呼吸功能、线粒体呼吸酶、超氧化物歧化酶(SOD)、丙二醛(MDA)、Ca2+等。结果大鼠MCAO后24 h,脑线粒体损伤明显,表现为肿胀、膜流动性降低,膜磷脂降解、呼吸功能衰减,呼吸酶、SOD活性降低,Ca2+、MDA含量升高;静脉注射20(S)-人参皂苷Rg3(5,10 mg.kg-1)能明显抑制缺血脑线粒体膜流动性的降低,膜磷脂降解,减少脑缺血引起的线粒体肿胀,抑制NADH脱氢酶、琥珀酸脱氢酶和细胞色素C氧化酶活性的降低,改善线粒体呼吸功能;同时20(S)-人参皂苷Rg3能明显降低脑缺血大鼠脑神经细胞线粒体MDA含量、升高SOD活性、抑制Ca2+过多摄入。结论20(S)-人参皂苷Rg3对缺血脑神经细胞线粒体的损伤有明显的保护作用,该作用可能与清除氧自由基、抑制脂质过氧化、拮抗Ca2+有关。
Aim To study the mitochondria-protective effects of 20 (S)-ginsenoside Rg3 on focal cerebral ischemia injuries and its mechanism in rats. Methods Middle cerebral artery occlusion (MCAO) was used to induce focal cerebral ischemia model. After 24 h occlusion, cortex mitochondria was isolated and prepared for the measurement of membrane fluidity, swelling, phospholipid content, respiratory function, activities of mitochondrial respiratory enzymes and superoxide dismutase ( SOD), contents of phospholipid, malondial dehyde (MDA) and Ca^2+ to evaluate the function of mitochondrial. Results Focal cerebral ischemia resuited in severe neuronal mitochondrial injuries, which could be alleviated by iv 20 (S)-ginsenoside Rg3 5 mg·kg^-1, 10 mg ·kg^-1, and nimodipine 1.0 mg· kg^-1. The swelling of mitochondria was ameliorated, the decomposability of membrane phospholipid was decreased,the membrane fluidity of mitochondria was increased. 20 (S)-ginsenoside Rgz also significantly inhibited the decrease in the activities of respiratory enzymes and SOD of mitochondrial, and the increase in MDA and Ca^2+ levels caused by cerebral ischemia in rats. Conclusion 20 (S)-ginsenoside Rg3 showed a protective action against the cortex mitochondrial injuries in rats induced by cerebral ischemia. The mechanisms may be derived from reducing lipid peroxides, inhibiting Ca^2+ overload, scavenging free radicals and improving the energy metabolism.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2006年第2期216-220,共5页
Chinese Pharmacological Bulletin
作者简介
田京伟(1976-),男,博士生,研究方向:心脑血管药理学,Tel:05352102138,E-mail:Tianjingwei@luye-pharm.com;
傅风华(1963-),男,教授,博士生导师,研究方向:精神神经药理学,Tel:0535-6706060,E-mail:Fenghua@luye.pharm.com