丹参酮对阿尔茨海默病样大鼠海马内诱导型一氧化氮合酶mRNA和乙酰胆碱酯酶表达的影响  

Influence of Tanshinone on levels of iNOS mRNA and AChE in brain of Alzheimer′s disease rat

作　　者：谢明[1] 成志[1] 

机构地区：[1]南华大学附属第一医院神经内科,湖南衡阳421001

出　　处：《中国现代医学杂志》2008年第8期1005-1007,1012,共4页China Journal of Modern Medicine

摘　　要：目的探讨丹参酮(Tan)对阿尔茨海默病(AD)样大鼠海马内诱导型一氧化氮合酶(iNOS)mR-NA及乙酰胆碱酯酶(AChE)表达水平的影响。方法60只SD大鼠随机分为3组,每组20只:对照组、模型组、治疗组。模型组与治疗组,在大鼠双侧海马齿状回背侧细胞带微量注射10μg凝聚态Aβ1-42以建立AD样记忆障碍的动物模型;建模24h后,用丹参酮(50mg/kg)对治疗组大鼠连续灌胃14d。采用以下方法观察丹参酮的干预效果:采用明暗箱被动回避法、穿梭法检测丹参酮对大鼠学习记忆功能障碍的改善作用;用半定量逆转录-聚合酶链反应(RT-PCR)方法测定海马内iNOSmRNA的表达;利用AChE组织化学方法观察大鼠海马内各亚区胆碱能纤维的变化。结果与对照组相比,模型组大鼠的学习记忆功能明显障碍,而给予丹参酮治疗后,可以有效延长大鼠进洞潜伏期(P<0.05),显著增加大鼠主动回避次数(P<0.05),减少逃避失败次数(P<0.05)。模型组大鼠海马内iNOS的表达上调,各亚区AChE阳性纤维面积百分比则显著低于对照组(P<0.01);治疗组中上述指标变化有不同程度的改善。结论丹参酮对Aβ1-42诱导大鼠的学习记忆功能障碍具有显著改善作用。其机制可能是保护AD样大鼠脑内胆碱能系统,并调节iNOS的表达。[Objective] To investigate the influence of Tanshinone on the levels of iNOS mRNA and AChE in the brain of AD rat and its potential therapeutic mechanism. [Methods] 60 Male Sprague Dawley rats were divided into three groups （20 rats for each）： control group, model group and treatment group. 10 μg Aβ1--42 was injected bilaterally into the dorsal lateral of the dentate gyms in the hippocampus of rats in the model group and the treatment group to prepare the AD models. 24 h after modeling, Tanshinone administration （50 mg/kg） was used by, gastric perfusion for rats in the treatment group. Later on, the RT-PCR analysis was used to detect the expression of iNOS in hippocampus of rats. The activity of AChE of each subregion in hippocampus of rats was determined by AChE histochemical technique. [Results] Learning and memory dysfunction was detected by the behavioural test after Aβ1-42 injection. After treatment with Tan, the latencies of passive avoidance test were markedly extended respectively in rats （P 〈0.05）, and the number of avoidance was increased and escape failure of rats were decreased in treatment group （P 〈0.05）. Both RT-PCR analysis and activity of AChE showed that the expression of iNOS in models was upregulated. The level of AChE positive fibers of each subregion in hippocampus after A131-42 injection decreased as compared with controls. With Tanshinone administration, the changes mentioned above were improved to vary degrees respectively. [Conclusion] Tan could obviously improve the impaired learning and memory induced by A131-42 in rats.

关 键 词：阿尔茨海默病 丹参酮 iNOS ACHE 

分 类 号：R964[医药卫生—药理学]