人参皂甙Rb3抗缺血低氧性脑损伤及其机制的研究  

PROTECTIVE EFFECTS OF GINSENOSIDE RB_3 ON HYPOXIC/ISCHEMIC BRAIN INJURY AND INVOLVED MECHANISMS

作　　者：沈洪妹[1] 张志军[2] 江山[2] 姜正林[2] 

机构地区：[1]苏州大学医学院基础医学系,江苏苏州215123 [2]南通大学航海医学研究所,江苏南通226001

出　　处：《中国应用生理学杂志》2006年第3期302-306,共5页Chinese Journal of Applied Physiology

摘　　要：目的:利用整体动物、离体海马脑片、原代培养的海马神经细胞作为实验对象,研究人参皂甙Rb3抗缺血低氧性脑损伤作用及相关机制。方法:①在密闭三角烧瓶中观察小白鼠低氧存活时间。②在离体海马脑片上观察顺向群锋电位(OPS)的恢复率、恢复程度及低氧损伤电位(HIP)出现率。③低压舱作为全脑低氧模型,采用NADPH-d法,观察一氧化氮合酶(NOS)阳性细胞数、平均光密度值。④采用原代培养海马神经细胞低氧模型,观察神经细胞形态、乳酸脱氢酶(LDH)漏出率及总NOS、结构型一氧化氮合酶(cNOS)、诱导型一氧化氮合酶(iNOS)活性。结果:①小白鼠低氧存活时间人参皂甙Rb3组较正常组明显延长,并具有剂量依赖性,以10 mmol/L组最为显著。②人参皂甙Rb3对海马脑片缺血时CA1区诱发场电位的影响:对照组海马脑片模拟缺血时全部出现HIP,复氧供糖1h后OPS恢复率为0%,OPS恢复程度平均为缺血前的5.42%。使用人参皂甙Rb3后,HIP出现率明显下降,复氧供糖1 h后OPS恢复率、OPS恢复程度均增加,以60μmol/L作用最为显著。③人参皂甙Rb3使海马CA1区锥体细胞层NOS阳性细胞数、平均光密度值下降。④人参皂甙Rb3能使细胞外液中LDH的漏出减少、总NOSi、NOS活性下降。结论:人参皂甙Rb3对缺血低氧性脑损伤有保护作用,并具有剂量依赖性,作用机制可能与降低低氧损伤时细胞膜通透性,减少NOS表达,抑制NOS的活性,尤其是诱导型NOS活性有关。Aim： To observe protective effects and involved mechanism of ginsenoside Rb3 on hypoxic/ischemic brain injury, using cultured hippocampal neurons, rat hippocampal slices and intact animals. Methods： ①Mice were tightly closed in glasses of 150 ml, and then survival time of them was observed. ②During simulated ischemia and after reoxygenation, changes of orthodromic population spikes （OPS） in the area CA1 of hippocampal slice were investigated. ③By using histochemistry, the expressions of NOS in CA1 area of rat hippocampus after hypoxic exposure were observed. ④Using LDH detection, tests of total NOS, iNOS and cNOS activity, the protective effects of ginsenoside Rb3 were investigated on cultured hippocampal neurons treated with hypoxia. Results： ①Given ginsenoside Rb3 （10 mmol/L）, mice survived significantly longer than that of control group. ②The occurrence of HIP （hypoxic injury potentials） decreased after administration of ginsenosides Rb3 （60 μmol/L） in many slices, while the recovery rate and amplitude of OPS after reoxygenation were significantly higher than those of the control group. ③In CA1 area of rat hippocampus, NO.S-positive neurons increased at the end of 24 h hypoxia and further 24 h reoxygenation, while the number of NOS-positive neurons decreased after treatment with ginsenoside Rb3. ④The LDH leakage rate of cultured rat hippocampal neurons increased at the end of hypoxia, while it decreased after treatment with Rb3. Moreover the total NOS, especially iNOS activity of these neurons also decreased. Conclusion： Ginsenoside Rb3 has a significant protective effect on hypoxic-ischemic injury of neurons, and this involves the stabilization of the cell membrane, the inhibition of the expression and activity of NOS, especially iNOS activity.

关 键 词：人参皂甙Rb3 缺血低氧性脑损伤 顺向群锋电位 乳酸脱氢酶 一氧化氮合酶 

分 类 号：R339.5[医药卫生—人体生理学]