目的探讨中药丹参酮ⅡA(TanⅡA)对AD模型大鼠学习记忆、海马内基质金属蛋白酶(MMP-2)、诱导型一氧化氮合酶(iNOS)表达及自由基释放的影响及作用机制。方法采用β-淀粉样蛋白(Aβ)定向注射法建立AD大鼠模型,并使用TanⅡA干预,通过观察大鼠学习记忆能力、定量分析大鼠海马MMP-2和iNOS基因及蛋白表达差异及表达相关性、自由基释放量的影响以阐明其作用机制。结果与正常对照组相比,Aβ注射法所建立AD模型大鼠海马内iNOS及MMP-2的表达显著增高(P<0.05),两者的表达在mRNA及蛋白水平均正相关(P<0.05)。AD大鼠海马内诱导释放的一氧化氮(NO)、ONOO-及活性氧(ROS)自由基含量显著增高(P<0.05),同时AD模型组大鼠的学习记忆能力明显下降。而TanⅡA(50mg/kg)干预可显著降低AD大鼠海马内的NO、ONOO-及ROS含量,并降低iNOS(P<0.05)及MMP-2蛋白的表达(P<0.01),明显改善AD模型大鼠的学习记忆能力。结论TanⅡA可有效缓解AD症状,作用机制可能与抑制AD诱导的iNOS及MMP-2蛋白的表达,减少氧化性毒害自由基的产生,抑制氧化应激损伤有关。 Objective To investigate the effect and mechanism of TanⅡA on learning and memory, expression of matrix metalloproteinase (MMP-2), iNOS and free radical in hippocampus of AD model rats. Methods A rat model of Alzheimer ’s disease (AD) was established by direct injection of β - amyloid protein (Aβ). TanⅡA intervention was used to observe the learning and memory abilities of rats. Quantitative analysis of the expression of MMP - 2 and iNOS gene and protein in the hippocampus of rats Sexual, free radical release to clarify its mechanism of action. Results Compared with the normal control group, the expression of iNOS and MMP-2 in hippocampus of AD model rats induced by Aβ injection were significantly increased (P <0.05), and the expressions of both mRNA and protein were positively correlated with each other (P <0.05 ). The contents of NO, ONOO- and reactive oxygen species (ROS) in hippocampus of AD rats were significantly increased (P <0.05), and the learning and memory abilities of AD model rats were significantly decreased. However, TanⅡA (50mg / kg) significantly decreased NO, ONOO- and ROS content in hippocampus and decreased iNOS (P <0.05) and MMP-2 protein Learning and memory in rats. Conclusions TanⅡA can effectively alleviate the symptoms of AD. The mechanism may be related to inhibiting the expression of iNOS and MMP-2 protein induced by AD, reducing the production of oxidative toxic free radicals and inhibiting the oxidative stress injury.