金钗石斛总生物碱对Aβ_(25-35)所致大鼠海马组织Aβ含量的影响

Effect of Dendrobium nobil Lindl.Alkaloids on the product of Aβ in hippocampus of rats induced by Aβ_(25-35)

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）.