| 摘要: |
| 目的 探讨中药丹参酮Ⅱ A(Tan Ⅱ A)对AD模型大鼠学习记忆、海马内基质金属蛋白酶（MMP2）、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Tan Ⅱ A干预，通过观察大鼠学习记忆能力、定量分析大鼠海马MMP2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MMP2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Tan Ⅱ A(50 mg/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MMP2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 Tan Ⅱ A可有效缓解AD症状，作用机制可能与抑制AD诱导的iNOS及MMP2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。 |
| 关键词: 阿尔茨海默病 基质金属蛋白酶2 诱导型一氧化氮合酶 丹参酮Ⅱ A |
| DOI：10.3724/SP.J.1008.2010.0380 |
| 投稿时间：2009-11-23修订日期：2010-04-01 |
| 基金项目: |
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| Effect of tanshinone Ⅱ A on MMP 2 and iNOS expression and free radical release in hippocampus of rat Alzheimer’s disease model |
| JIANG Ping, CHEN Ming, L Jun, CHEN Chong, JIAO Binghua* |
| (Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433, China) |
| Abstract: |
| Objective To investigate the influence of tanshinone Ⅱ A on learning and memory ability, expression of inducible nitric oxide synthase (iNOS), matrix metalloproteinase Ⅱ (MMP2) and release of free radicals in the hippocampus of rat Alzheimer’s disease (AD) model, and to explore the related mechanism. Methods Rat AD models were established by direct βamyloid protein (Aβ) injection method. For tanshinone Ⅱ A (Tan Ⅱ A) intervention test, the learning and memory ability of the AD rats were observed, the expressions of iNOS, MMP2 at gene and protein levels were determined and their correlation were analyzed, and the release of free radical in the hippocampus region of AD rats was quantified. Results The expressions of iNOS and MMP2 in the hippocampus region of AD rats were significantly higher than that in the control group (P<0.05), and the expressions of iNOS and MMP2 were positively correlated at both mRNA and protein levels (P<0.05). Meanwhile, nitric oxide (NO), ONOO and reactive oxygen species (ROS) release in the hippocampus of AD rats were significantly higher than those in the control rats (P<0.05). The learning and memory ability was obviously decreased in AD model rats. Tan Ⅱ A intervention (50 mg/kg) significantly reduced the ADinduced release of NO, ONOO, and ROS, and expression of iNOS (P<0.05) and MMP2 protein (P<0.01) in the hippocampus region; it also greatly improved the learning and memory ability of AD model rats. Conclusion Tan Ⅱ A can effectively alleviated the AD symptoms, possibly by inhibiting ADinduced iNOS and MMP2 expressions, reducing toxic free radical, and suppressing oxidative injury in AD rats. |
| Key words: Alzheimer’s disease matrix metalloproteinase 2 nitric oxide synthase tanshinone Ⅱ A |
