丹参酮对于阿尔茨海默症大鼠颞叶iNOS，MMP-2 表达的 影响及机理研究

目的：应用中药丹参酮(tanshinone II A，Tan II A)治疗AD大鼠，观察TanⅡ A 干预前后，AD大鼠学习记忆、颞叶中诱导型一氧 化氮合成酶(iNOS)、基质金属蛋白酶（MMP-2）表达的变化。方法：采用beta- 淀粉样蛋白（A beta）定向注射法建立AD大鼠模型，并使用 Tan II A 干预，通过避暗测试、real-time PCR和Western Blot 分别观察大鼠学习记忆能力、大鼠颞叶MMP-2、iNOS 两者的mRNA 及蛋白表达的变化。应用SPSS13.0 进行统计学分析。结果：与假手术组相比，AD 组的平均潜伏期缩短（P＜0.01），平均错误次数 增加（P＜0.01），差异均有统计学意义。颞叶内iNOS、MMP-2 mRNA 表达均显著增高（P＜ 0.01, P＜0.01）；两蛋白的表达均显著增 高（P＜0.01, P＜0.01）。与AD组相比，Tan IIA 组的平均潜伏期延长（P＜0.01），平均错误次数减少（P＜0.01），差异均有统计学意 义。颞叶内iNOS、MMP-2 mRNA表达均显著下降（P＜0.05, P＜0.05），两蛋白的表达均显著下降（P＜0.01, P＜0.01）。结论：Tan II A 干预可显著降低AD 大鼠颞叶中iNOS、MMP-2 mRNA及蛋白的表达，显著改善AD 大鼠的学习记忆能力。其作用机制可能是 通过降低A-beta诱导的iNOS及MMP-2 的表达，抑制氧化应激损伤来完成。

The Effect of Tanshinone on the Expression of iNOS, MMP-2 in Temporal of Alzheimer's Disease Model Rats and Study on Mechanism

Objective:To investigate the influence of tanshinone IIA (Tan II A) on the learning and memory ability, the expression of the inducible nitric oxide synthase (iNOS), matrix metalloproteinase II (MMP-2) in temporal of Alzheimer''s disease (AD) model rats.Methods:AD model rats were established by direct beta-amyloid protein (A beta) injection method. For Tan IIA intervention test, the learning and memory ability of AD rats were observed by passive avoidance task test, the expression of iNOS, MMP-2 at mRNA and protein levels in temporal region were compared by real-time PCR and Western Blot respectively. Using SPSS 13.0 to statistic analyse the data.Results:Compared with sham-operation group, the average latency time of passive avoidance task test in AD group was decreased (P< 0.01), and the average wrong times of passive avoidance task test in AD group was significantly increased (P< 0.01). Both mRNA and protein expressions of iNOS, MMP-2 in temporal were significantly increased (mRNA:P< 0.01, P< 0.01; protein: P<0.01, P<0.01). Compared with AD group, the average latency time in Tan II A group was significantly increased (P<0.01), and the average wrong times in Tan IIA group was significantly decreased(P<0.01). Both mRNA and protein expressions of iNOS, MMP-2 of temporal in Tan IIA group were significantly decreased respectively (mRNA:P<0.05, P<0.05; protein: P< 0.01, P< 0.01).Conclusion:Tan II A can effectively enhance the ability of learning and memory of AD rats, significantly decrease mRNA and protein expressions of iNOS, MMP-2 in temporal of AD rats. This mechanism is probably inhibiting iNOS and MMP-2 expressions induced by A-beta in AD rats through suppressing oxidative injury.