年龄因素对3-硝基丙酸预处理对神经保护作用的实验研究

Aging attenuates the neuroprotective effect by preconditioning with 3-nitropropionic acid

目的 研究年龄因素对 3 硝基丙酸 (3 NPA)诱导神经保护作用的影响及其腺苷受体相关机制。 方法 观察不同月龄小鼠经 3 NPA预处理后 ,海马脑片CA1区神经元群峰电位波幅(PSA)在缺氧和恢复供氧后的变化及选择性腺苷A1、A2a受体激动剂和拮抗剂对PSA缺氧后恢复的影响。 结果 成年鼠 3 NPA预处理后PSA缺氧后恢复由对照组的 2 6 1%± 12 2 %增至 92 9%±15 3 % (P <0 0 1) ,老龄鼠由 17 2 %± 9 6 %仅增至 5 3 5 %± 11 5 % (与对照组比较P <0 0 5 ,与成年3 NPA组比较P <0 0 5 )。腺苷A1受体激动剂N6 环戊腺苷灌流脑片同样能促进PSA缺氧后恢复 ,且增高幅度亦呈年龄依赖模式 ;A1受体拮抗剂 8 环戊基 1,3 二丙基黄嘌呤可完全抑制 3 NPA预处理导致的PSA缺氧后恢复的增高。 结论 3 NPA预处理在成年和老年小鼠均可使神经元缺氧耐受性的增高 ,其神经保护作用受老龄因素的影响而减弱。腺苷A1受体激活参与 3 NPA预处理过程 ,并受年龄因素的影响。

Objective To investigate the effect of aging on neuroprotection by preconditioning with 3-nitropropionic acid (3-NPA) and the relationship between aging and adenosine receptor. Methods Population spike amplitude (PSA) in region CA 1 in hippocampal slices was measured during 15 min hypoxia and 45 min posthypoxic recovery from adult and aged mice, which were pretreated in vivo with a single intraperitoneal injection of 3-NPA (20 mg/kg). Posthypoxic PSA recovery was also observed after perfusion with selective agonist or antagonist of adenosine A 1 and A2a receptors. Results Posthypoxic recovery of PSA increased from 26.1±12.2% in control slices to 92.9±15.3% in pretreated slices from adult (P<0.01), and from 17.2±9.6% in control slices to 53.5±11.5% in pretreated slices from aged mice (P<0.05 vs control, P<0.05 vs pretreated slices from adult), respectively. In slices, which were perfused with 50 nM N6-cyclopentyladenosine, an agonist of selective adenosine A 1 receptors, posthypoxic recovery of PSA improved in an age-dependent manner as in slices, which were in vivo pretreated with 3-NPA. 100 nM 8-cyclopentyl- 1,3-dipropylxanthine, a selective antagonist of adenosine A 1 receptors, completely reversed the increase of posthypoxic PSA recovery in 3-NPA pretreated slices. Conclusions We conclude that 3-NPA increases neuronal hypoxic tolerance not only in adult mice, but also in aged mice; whereas neuroprotection by preconditioning with 3-NPA is attenuated by aging. Activation of adenosine A 1 receptor contributes to the 3-NPA induced neuroprotective effect and is involved in age-difference by preconditioning.