摘要
目的:考察积雪草苷对阿尔茨海默病(AD)模型大鼠海马组织中过氧化物酶体增殖物激活受体γ(PPAR-γ)蛋白表达的影响。方法:将SD大鼠随机分为假手术组、模型组、阳性对照组(多奈哌齐片,1 mg/kg)和积雪草苷低、中、高剂量组(5、15、45 mg/kg),每组10只。除假手术组外,其余各组大鼠采用脑内注射β-淀粉样肽1-42(Aβ_(1-42))复制AD模型。假手术组和模型组大鼠ig等体积生理盐水,各给药组大鼠ig相应药物,每天1次,连续2周。采用Morris水迷宫实验检测大鼠空间记忆能力;免疫组化检测海马组织中Aβ_(1-42)沉积情况;酶联免疫吸附法检测海马组织中白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)表达;Western blot法检测海马组织中PPAR-γ蛋白表达情况。结果:与假手术组比较,模型组大鼠空间记忆能力减弱,表现为平均潜伏期延长、跨越原平台次数减少(P<0.05或P<0.01);海马组织中IL-6、TNF-α和PPAR-γ蛋白表达均增加,Aβ_(1-42)大量沉积(P<0.01)。与模型组比较,各给药组大鼠空间记忆能力提高,表现为平均潜伏期缩短、跨越原平台次数增加(P<0.05或P<0.01);海马组织中IL-6和TNF-α表达减少,PPAR-γ蛋白表达增加,Aβ_(1-42)沉积减少(P<0.01)。结论:积雪草苷可能通过促进海马组织PPAR-γ蛋白的表达和抑制炎症因子IL-6、TNF-α的表达来改善AD模型大鼠的空间记忆能力。
OBJECTIVE：To observe the effects of asiaticoside on peroxisome proliferator activated receptor gamma（PPAR-γ）protein expression in hippocampal tissue of Alzheimer disease（AD）model rats.METHODS：SD rats were randomly divided into sham operation group,model group,positive control group（Donepezil tablets,1 mg/kg）and asiaticoside low-dose,medium-dose and high-dose groups（5,15,45 mg/kg）,with 10 rats in each group.Except for sham operation group,those groups were given intracerebral injection of Aβ1-42 to induce AD model.Sham operation group and model group were given constant volume of normal saline intragastricaly,and treatment groups were given relevant medicine intragastrically,once a day,for consecutive 2 weeks.Spatial memory ability of rats was detected by Morris water maze test;Aβ1-42 deposition in hippocampus tissue was detected by immunohistochemical method;the expressions of IL-6 and TNF-α in hippocampus tissue were detected by ELISA;the protein expression of PPAR-γ in hippocampus tissue was detected by Western blot assay.RESULTS：Compared with sham operation group,spatial memory ability of rats was retarded in model group,manifesting as average incubation period was prolonged and the times of crossing original platform decreased（P〈0.05 or P〈0.01）;the expression of IL-6 and TNF-α in hippocampus tissue were increased while that of PPAR-γ was decreased,and Aβ1-42 deposition was greatly increased（P〈0.01）.Compared with model group,spatial memory ability of rats was improved in treatment groups,manifesting as average incubation period was shortened and the times of crossing original platform increased（P〈0.05 or P〈0.01）;the expression of IL-6 and TNF-α in hippocampus tissue were decreased,while that of PPAR-γ was increased,and A β1-42 deposition was decreased（P〈0.01）.CONCLUSIONS：Asiaticoside can improve spatial memory ability of AD model rats by improving the expression of PPAR-γ in hippocampus tissue and inhibiting the expression of IL-6 and TNF-α.
出处
《中国药房》
CAS
北大核心
2016年第34期4791-4794,共4页
China Pharmacy
基金
泸州市科技局-泸州医学院联合课题(No.2013LZLYJ52)
