摘要
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 influence of tanshinone Ⅱ A on learning and memory ability,expression of inducible nitric oxide synthase（iNOS）,matrix metalloproteinase Ⅱ（MMP-2） 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 β-amyloid 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,MMP-2 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 MMP-2 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 MMP-2 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 AD-induced release of NO,ONOO-,and ROS,and expression of iNOS（P 0.05） and MMP-2 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 AD-induced iNOS and MMP-2 expressions,reducing toxic free radical,and suppressing oxidative injury in AD rats.
出处
《第二军医大学学报》
CAS
CSCD
北大核心
2010年第4期380-384,共5页
Academic Journal of Second Military Medical University
