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作 者:张明辉[1] 李菲[1] 张玮[1] 吴芹[1] 石京山[1]
机构地区:[1]遵义医学院药理学教研室暨基础药理省部共建教育部重点实验室,贵州遵义563099
出 处:《遵义医学院学报》2016年第1期18-21,共4页Journal of Zunyi Medical University
基 金:国家自然科学基金资助项目(NO:30660208);贵州省科技基金资助项目(NO:黔科合JZ字[2014]2016);贵州省教育厅自科项目(NO:黔教科2010043);遵义医学院院招标课题基金项目(NO:F-612)
摘 要:目的观察金钗石斛总生物碱(Dendrobium nobil Lindl.Alkaloids,DNLA)对β-淀粉样蛋白(Aβ_(25-35))诱导的大鼠痴呆模型海马组织Aβ含量的影响。方法雄性Sprague-Dawley大鼠随机分为4组:假手术组、模型组、DNLA低剂量(40 mg/kg/d)及高剂量组(80 mg/kg/d)。预给药7 d后,双侧海马注射Aβ_(25-35)(1μg/μL,5μL),假手术组注射同体积生理盐水,术后继续灌胃14 d,Morris水迷宫检查大鼠空间学习成绩,Western blot法检测海马组织Aβ_(1-42)含量,β淀粉样前体蛋白(APP)和β淀粉样蛋白前体蛋白裂解酶1(BACE1)的蛋白表达。结果双侧海马注射Aβ_(25-35)后,模型组大鼠空间学习成绩明显比假手术组差,给予DNLA后可改善大鼠空间学习成绩;模型组大鼠海马Aβ_(1-42)、APP和BACE1蛋白量均明显高于假手术组;与模型组比较,DNLA给药可明显减少海马组织Aβ_(1-42)的含量,降低APP和BACE1蛋白在海马组织的表达(P<0.05)。结论 DNLA具有改善Aβ_(25-35)所致大鼠痴呆模型的作用,可能与减少海马组织Aβ_(1-42)产生有关。Objective To observe the effect of Dendrobium nobil Lindl. Alkaloids( DNLA) on the production ofβ-amyloid( Aβ_(1-42)) in hippocampus of rats induced by Aβ_(25-35). Methods Forty Sprague-Dawley rats were randomed into four groups: sham,model,DNLA 40 mg / kg / d and 80 mg / kg / d groups. Rats were orally pre-treated with different doses of DNLA for 1 week,and then model rats were injected 5 μl Aβ_(25-35)( 1 μg /μl) into the lateral hippocampus,sham rats were injected equal volume of normal saline instead of Aβ. After operation rats were given DNLA or distill water for another 2 weeks. Morris water maze was used to test the spatial learning performance of rats; the content of Aβ_(1-42) and the protein expression of β-amyloid precursor protein( APP)and β-site amyloid precursor protein-cleaving enzyme 1( BACE1) in hippocampi were assayed by western blot. Results After injecting Aβ_(25-35) into hippocampus,model rats decreased the spatial learning capability compared with sham rats,rats treated with DNLA significantly improved the performance. The content of Aβ_(1-42) and the protein expression of APP and BACE1 in hippocampus of model rats were significantly increased. However,the content of Aβ_(1-42) and the protein expression of APP and BACE1 were reduced in the hippocampi of DNLA-treated rats. Conclusion DNLA could ameliorate the spatial learning performance of Aβ_(25-35) induced AD rat model,and this effect may be related to decreases in generation of Aβ_(1-42).
关 键 词:金钗石斛总生物碱 Β-淀粉样蛋白 Β淀粉样前体蛋白 β淀粉样蛋白前体蛋白裂解酶1 大鼠
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