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出 处:《解剖学报》2013年第3期313-317,共5页Acta Anatomica Sinica
基 金:山东省自然科学基金资助项目(R2010HM132);山东省科技厅博士基金资助项目(BS2010YY072)
摘 要:目的研究乙酰葛根素对β-淀粉样肽1-42(Aβ1-42)海马立体定位注射所致阿尔茨海默病(AD)模型大鼠的药物作用和对炎症因子蛋白激酶C-δ(PKC-δ)、白细胞介素-6(IL-6)表达的影响。方法将40只Wistar大鼠随机分为对照组、模型组、乙酰葛根素低、高剂量组。用Aβ1-42双侧海马注射制备AD大鼠模型,Morris水迷宫测定不同时期各组大鼠的学习记忆能力,ELISA测定血清IL-6含量的变化,Western blotting测定PKC-δ表达的变化。结果模型大鼠应用Aβ1-42注射14d后,Morris水迷宫逃避潜伏期与术前及对照组比较显著延长,穿越平台次数显著减少(P<0.01);应用乙酰葛根素10d后,血清中IL-6的表达量模型组显著高于对照组、乙酰葛根素低、高剂量组(P<0.01);海马匀浆中PKC-δ的表达量模型组显著高于对照组、乙酰葛根素低、高剂量组,乙酰葛根素低、高剂量组表达仍高于对照组(P<0.05)。结论乙酰葛根素能显著改善阿尔茨海默病模型大鼠的学习记忆能力,对阿尔茨海默病有显著的预防和保护作用,机制可能与调控PKC-δ/Caspase通路,抑制β-淀粉样肽的神经毒性,降低PKC-δ、IL-6的表达,从而发挥抗痴呆的作用。Objective To investigate the effect of acetylpuerarin on the expression of inflammation factors of protein kinase C (PKC-δ) and interferon-6 (IL-6) at the hippocampus stereotactic injection of Aβ1-42. Methods Forty Wistar rats were randomly divided into the control group, AD model group, acetylpuerarin low-dose group and high-dose group. AD model rat was produced by bilateral hippocampal injection of Aβ1-42. Learning and memory of the rat was tested through the method of Morris water maze, ELISA was used to determine the expression of IL-6 and Western blotting to detect the changes of PKC-δ. Results Fourteen days after Aβ1-42 injection, Morris water maze escape latency was more extended than pre-surgery and control group, and the times of crossing the platform were significant reduction (P 〈 0. 01 ). After application aectylpueraria for 10 days, in the model group the expression of IL-6 in the serum was significantly higher than the control group, acetylpuerarin low -dose group and high-dose group (P 〈 0. 01 ) ; The amount of the expression of PKC-δ in the hippocampal homogenate of model group was significantly higher than the control group, acetylpuerarin low -dose group and high-dose group, but the expression of PKC-δ in the acetylpuerarin low -dose group and high-dose group was higher than the control group (P 〈 0.05). Conclusion Acetylpuerarin can significantly improve the learning and memory ability of AD rats. It has obvious preventive and protective effect on Alzheimer disease. The possible mechanism may be that acetylpueariu can regulate and control the Caspase pathway, attenuate the neurotoxicity of β-amyloid peptide, and reduce PKC-δ and IL-6 expression, and thus plays the role of anti-dementia.
关 键 词:乙酰葛根素 Β-淀粉样肽 阿尔茨海默病 蛋白激酶C-δ 白细胞介素-6 Morris水迷宫 酶联免疫吸 附试验 大鼠
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