摘要
目的探讨类叶升麻苷(acteoside,AS)对阿尔采末病(Alzheimer’s disease,AD)小鼠皮层组织中Caspase-3基因表达的影响。方法将昆明(kunming,KM)小鼠随机分为正常组,模型组,vitamin E(Vit E)组,类叶升麻苷低、中、高剂量组。除正常组外,其余各组小鼠均腹腔注射60 mg·kg-1·d-1的D-半乳糖和灌胃5 mg·kg-1·d-1的三氯化铝,连续造模60 d以制备AD模型。然后给以30、60、120 mg·kg-1·d-1的AS治疗30 d,期间造模继续。给药完成后,利用跳台法测定小鼠的学习和记忆能力,化学比色法测定小鼠血清及脑组织中的ACh E活性;HE染色观察各组小鼠皮层组织结构变化;免疫组化分析小鼠皮层组织中caspase-3基因表达的变化。结果与模型组相比,AS给药组小鼠的学习记忆能力有所改善,其下台潜伏期和错误次数均明显延长和减少(P<0.05或P<0.01),血清和脑组织中ACh E活性明显降低(P<0.05或P<0.01),皮层组织中神经细胞的形态和数量明显改善(P<0.01),且皮层组织中caspase-3基因表达明显下调(P<0.05或P<0.01)。结论 AS对D-半乳糖联合三氯化铝诱导的小鼠脑损伤具有明显保护作用,其保护机制可能是通过抑制小鼠皮层组织caspase-3基因表达,进而维持皮层组织神经细胞的正常形态及数量。
Aim To investigate the effect of acteoside （AS）on the expression of caspase-3 in cerebral cortex of mouse models of Alzheimer’s disease（AD）.Meth-ods Kunming （KM）strain mice were assigned into control group,model group,positive control group （VitE）and acteoside group.Every group was induced by a combination of D-galactose（i.p.60mg＆#183;kg -1 ＆#183; d -1 ）and AlCl3 （i.g.5mg＆#183;kg -1 ＆#183;d -1 ）for 60ds ex-cept for control group,then mice were treated by dif-ferent concentrations（30,60,1 20 mg＆#183;kg -1 ＆#183;d -1 ）of acteoside for 30ds.During the time,mice were in-duced continuously by a combination of D-galactose and AlCl3 .The learning and memory of mice were de-tected by step-down test,the activity of AChE in serum and brain of mice was measured by chemical colorime-try,the structure changes in cerebral cortex were ob-served by HE staining,and the expression of caspase-3 in cerebral cortex was analyzed through the immunohis-tochemical staining.Results Compared with model group,acteoside could improve the learning and mem-ory abilities（P〈0.05 or P〈0.01 ）,decrease the ac-tivity of AChE in serum and brain（P〈0.05 or P〈0.01 ）,and improve the morphology and number of neuron in cerebral cortex（P〈0.01 ）.Moreover,acte-oside could significantly inhibit the expression of caspase-3 in cerebral cortex （P〈0.05,P〈0.01 ）. Conclusion Acteoside has significantly protective effects on brain damage of mice induced by a combina-tion of D-galactose and AlCl3 , and it′s protective mechanism probably relate to inhibiting the expression of caspase-3 and maintainings the normal morphology and number of neuron in cerebral cortex.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2014年第12期1763-1768,共6页
Chinese Pharmacological Bulletin
基金
新疆维吾尔自治区科研机构创新发展基金项目(No2012015)
