贯叶金丝桃素衍生物GF1029体外抗AD活性及对AD模型大鼠行为学的影响

目的探讨贯叶金丝桃素衍生物GF1029对大鼠原代培养皮层细胞的保护作用及对衰老模型小鼠空间探索能力和脑抗氧化酶的影响。方法采用大鼠原代培养皮层细胞,用MTT法观察GF1029对100 nmol/L H2O2及20μmol/LAβ25-35损伤后的神经细胞的生长情况。用Aβ25-35侧脑室注射联合D-半乳糖腹腔注射的SD大鼠痴呆模型,经GF1029处理后,用Morris水迷宫实验(MWM)检测大鼠学习记忆能力;并取脑测定脑中丙二醛(MDA)含量和超氧化物歧化酶(superoxide dismutase,SOD)的活性。结果 GF1029在40及80μmol/L预处理2 h可减轻对H2O2及Aβ25-35诱导的大鼠皮层神经细胞损伤,GF1029在30、60 mg/kg灌胃可延长模型大鼠的逃避潜伏期(P<0.05),延长平台所在象限的停留时间(P<0.05),和增加跨平台次数(P<0.05),并可提高小鼠脑SOD活性,减少MDA含量(P<0.05)。结论贯叶连翘衍生物GF1029对H2O2及Aβ25-35诱导的大鼠皮层神经细胞损伤有保护作用,并可改善痴呆模型大鼠学习记忆,对抗神经系统衰老,提高脑组织抗氧化能力,抑制脂质过氧化损伤可能是其抗衰老机制之一。

Hyperforin derivative GF1029 in vitro anti-AD activity and effects on behavioral AD model rats

Objective To evaluate the effects of GF1029 on protection of primary cultured rat cortial neurons and the ability of learning and memory,activity of superoxide dismutase(SOD) and content of malondialdehyde(MDA)at brain tissue in model rat.Methods Primary culture SD rat cortical neurons was treated with 100 nmol/L H2O2 or 20 μmol/L Aβ25-35 to establish the Alzheimer's disease models.Cell viability of cortical neurons treated with different concentration of GF1029 was identified by MTT then AD rat models were established by lateral ventricle injection of Aβ25-35 and D-galactose injection.Meantime,the rats were administration of the GF1029.The spatial learning and memory capacity of experimental rats was examined by the morris water maze(MWM),The content of the MDA and activity of SOD were examined in the cerebral cortex.Results Cell viability of cortical neurons was increased in 100 nmol/L H2O2 or 20 μmol/L Aβ treated primary cultured cortical neurons.after pretreated with 30 60μmol/L GF1029 for 2 h.After treatment of the GF1029 at 30、60 mg/kg,the AD model rats exhibited a significant decrease in escape latencies(P<0.05),an increase in the time of staying the quadrants of platform(P<0.05),and the number of crossing over a platform compared with the model group,while the content of MDA decreased(and the activity of SOD increased.Conclusion The GF1029 protect the cortical neuron from H2O2 or Aβ25-35 toxic,and could improve the spatial learning and memory capacity and prevent the aging of central nervous systems in AD model rats,which may be related to its antioxidant effects and.