20(S)-人参皂苷Rg_3对脑缺血大鼠脑线粒体损伤的保护作用

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。

Protective effect of 20(S)-ginsenoside Rg3 against rat cortex mitochondrial injuries induced by cerebral ischemia

Aim To study the mitochondria-protective effects of 20(S)-ginsenoside Rg_3 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 resulted in severe neuronal mitochondrial injuries,which could be alleviated by iv 20(S)-ginsenoside Rg_3 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 Rg_3 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 Rg_3 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.