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 IIA 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 ofAlzheimer'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 expressionof 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 learningand memory ability of AD rats were observed by passive avoidance task test, the expression of iNOS, MMP-2 at mRNA and proteinlevels 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 andprotein expressions of iNOS, MMP-2 in temporal were significantly increased (mRNA:P< 0.01, P< 0.01; protein: P<0.01, P<0.01). Comparedwith AD group, the average latency time in Tan II A group was significantly increased (P<0.01), and the average wrong times inTan IIA group was significantly decreased(P<0.01). Both mRNA and protein expressions of iNOS, MMP-2 of temporal in Tan IIA groupwere significantly decreased respectively (mRNA:P<0.05, P<0.05; protein: P< 0.01, P< 0.01).Conclusion:Tan II A can effectively enhancethe ability of learning and memory of AD rats, significantly decrease mRNA and protein expressions of iNOS, MMP-2 in temporalof AD rats. This mechanism is probably inhibiting iNOS and MMP-2 expressions induced by A-beta in AD rats through suppressingoxidative injury.