天麻素对老年痴呆动物模型的抗氧化作用及其机制

目的构建β-淀粉样肽(1-40)(Aβ1-40)联合D-半乳糖(D-gal)致痴呆模型,探讨天麻素抗氧化的分子机制。方法成年雄性SD大鼠36只,侧脑室注射Aβ1-40联合腹腔注射D-gal构建SD大鼠痴呆模型,并同时给予天麻素预防性治疗,采用Morris水迷宫实验(MWM)进行行为学检测,用化学比色法检测大脑皮质过氧化氢(H2O2)及还原型谷胱甘肽(GSH)和谷胱甘肽还原酶(GR)的含量。用免疫印迹法检测大脑皮质中p38和P-p38的含量。结果痴呆模型组与对照组比较:逃避潜伏期明显延长(P0.05),在第Ⅲ象限逗留的时间明显减少(P0.05),跨越平台次数明显减少(P0.05),皮质H2O2的含量增加,皮质GSH和GR的含量降低(P0.05),P-p38表达增加(P0.05);而天麻素治疗后:与痴呆模型组相比,大鼠逃避潜伏期明显缩短(P0.05),在第Ⅲ象限逗留的时间明显增加(P0.05),跨越平台次数明显增加(P0.05),皮质H2O2的含量减少,皮质GR和GSH的含量升高(P0.05),P-p38表达减少(P0.05)。p38的表达在3组之间无差异(P0.05)。结论天麻素影响了痴呆模型大鼠皮质部分内源性巯醇抗氧化物(酶)如GSH和GR的含量,抑制了H2O2的产生,影响了P-p38的表达,对改善学习记忆能力,对抗大鼠神经系统的退行性变有一定的作用。

Antioxidation effects and mechanism of Gastrodin in AD rat models

To established β-amyloid peptide (1-40) (Aβ SUB>1-40/SUB>) and D-galactose(D-gal) AD rat models and to explore the anti-oxidation molecular mechanism of the Gastrodin and provide the experimental foundations for clinical treatment of AD. AD rat models were established by lateral ventricle injection of Aβ1-40 and abdominal cavity injection of D-gal (100 mg/kg) to thirty six male SD rats. Meantime, the rats were treated by intragastric administration the Gastrodin. Then the behavioral testing of experimental rats was performed by the Morris water maze(MWM). The thiol antioxidants including hydrogen peroxide (HSUB>2/SUB>O SUB>2/SUB>), glutathione reductase (GR) and glutathion (GSH) activities were examined by colorimetric method. The concentration of the p38 and P-p38 was examined respectively by Western blotting. The AD model rats when compared with control group exhibited a significant increase in escape latencies (EM> P/EM> <0.05), and a decrease in the time of staying at the third quadrants of platform and the degree of crossing over a platform. The cerebral cortex concentration of the H2O2 was increased, and the concentrations of the GR and GSH were decreased ( EM>P /EM><0.05). The expression of P-p38 was increased (EM> P/EM> <0.05). After the treatment with Gastrodin, the AD model rats exhibited a significant decrease in escape latencies ( EM>P /EM><0.05), an obvious increase in the time of staying the third quadrants of platform ( EM>P/EM> <0.05) and the increase of crossing over a platform (EM> P/EM> <0.05) when compared with the AD group ( EM>P /EM><0.05). The concentration of the H2O2 was decreased, the concentrations of GR and GSH were increased ( SUP>P /SUP><0.05). The expression of the P-p38 was less than that of the AD model ( EM>P /EM><0.05). But there were no significant differences between the three groups in the expression of the p38 ( EM>P/EM> >0.05). Gastrodin could improve the oriented learning and memory capacity and prevent the neurodegeneration of central nervous systems in AD model rats by partly affecting the expression of the thiol antioxidants(e.g. GR and GSH) and the expression o