摘要
目的 处于聚集及纤维丝状态的 β 淀粉样蛋白片段 1 - 4 2 (Aβ1 -4 2 )具有神经毒作用 ,可导致阿尔茨海默病 (AD)。本文观察蜕皮甾酮体外对Aβ1 -4 2 的聚集、纤维丝形成及其神经元毒性的影响 ,旨在为蜕皮甾酮防治AD提供依据。方法 透射电镜观察蜕皮甾酮及维生素E(VitE)对试管内Aβ1 -4 2 聚集和纤维丝形成的影响 ;MTT法及乳酸脱氢酶 (LDH)活性法检测培养的胚胎大鼠大脑皮层神经元存活率及神经元受损情况。结果 ① 1 0 0 μmol·L-1 Aβ1 -4 2 分别与磷酸盐缓冲液 (PBS)、1 0 0 μmol·L-1 蜕皮甾酮和 1 0 0 μmol·L-1 VitE孵育 3d时 ,各组均无纤维丝形成 ;孵育 7d时 ,各组均见纤维丝形成 ,但蜕皮甾酮和VitE组的纤维丝形成较PBS组明显减少 ,尤以蜕皮甾酮组更明显。2 0 μmol·L-1 的蜕皮甾酮和 2 0 μmol·L-1 VitE对Aβ1 -4 2 的聚集及纤维丝形成无明显影响。② 1 0 0μmol·L-1 的Aβ1 -4 2 作用 2 4h ,神经元存活率明显下降。蜕皮甾酮或VitE 1 0~ 1 0 0 μmol·L-1 预处理 30min,再与 1 0 0 μmol·L-1 的Aβ1 -4 2 作用 2 4h ,神经元的存活率呈剂量依赖性增加 ,LDH活性呈剂量依赖性降低。结论 离体条件下 ,蜕皮甾酮可直接抑制Aβ1 -4 2 的聚集及纤维丝形成 ,减轻Aβ1 -4 2 对神经元的毒性 ,?
AIM To study if ecdysterone can inhibit fibril-forma t ion and neurotoxicity of aggregated amyloid β-protein fragment 1-42 (Aβ 1 -42 ) in vitro. METHODS The aggregated Aβ 1-42 fibril-formation in tube was observed by a transmission electron microscope. The survival and injury of neurons from rat embryo cortex were measured by MTT assay and lactate dehydrogenase (LDH) activity. RESULTS ① 100 μmo l·L -1 Aβ 1-42 incubated with phosphate-buffered saline (PBS), 100 μmol·L -1 ecdysterone and 100 μmol·L -1 vitamine E (VitE), respec tively for 3 d, showed no aggregated fibril formation; incubated for 7 d, fibril formation was seen in each group, and more fibril formation was seen in Aβ 1-42 in the presence of PBS than that in the presence of ecdysterone or VitE . There was no difference in PBS, 20 μmol·L -1 ecdysterone and 20 μmol·L -1 VitE groups. ② When exposed to 100 μmol·L -1 Aβ 1 -42 for 24 h, the viability of neurons obviously decreased, but if pretreated with 10-100 μmol·L -1 ecdysterone or 10-100 μmol·L -1 VitE for 30 min, then exposed to 100 μmol·L -1 Aβ 1-42 for another 24 h , the neuron viability was increased, and the LDH release of neurons was decreas ed, both in a concentration-dependent manner. CONCLUSION In vitro, ecdysterone may directly inhibits fibril formation of Aβ 1-42 , and weaken the neurotoxicity of Aβ 1-42 .
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2003年第5期375-379,共5页
Chinese Journal of Pharmacology and Toxicology
基金
贵州省省长基金资助项目 (2 0 0 10 16)~~