丹参酮对阿尔茨海默病样大鼠海马内乙酰胆碱酯酶和一氧化氮合酶表达的影响  

Influence of Tanshinone on Levels of AChE and NOS in the Hippocampus after Aβ_(1-40) Hippocampal Injection of Rats with Alzheimer's-like Disease

作　　者：李龙宣[1] 林传友[1] 茹立强[1] 殷光甫[1] 

机构地区：[1]华中科技大学同济医学院基础医学院神经生物学系,武汉430030

出　　处：《华中科技大学学报（医学版）》2003年第1期19-23,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目 ( No.3 0 1710 82)

摘　　要：目的　探讨丹参酮治疗阿尔茨海默病 ( Alzheim er’s disease,AD)样大鼠的神经化学机制。方法　应用凝聚态 β-淀粉样肽 1～ 40片段 ( Aβ1～ 40 )在大鼠海马齿状回背侧进行微量注射以建立 AD样记忆障碍的动物模型 ;利用改良的乙酰胆碱酯酶 ( ACh E)组织化学方法观察大鼠海马内各亚区胆碱能纤维的变化 ;用免疫组织化学方法检测大鼠海马内神经元型一氧化氮合酶 ( n NOS)、诱导型一氧化氮合酶 ( i NOS)的表达。结果　大鼠双侧海马内注射 Aβ1～ 40 ( 2 0μg) 14d后 ,海马内各亚区 ACh E阳性纤维面积百分比显著低于对照组 ;海马内 i NOS的表达上调 ,而 n NOS的表达则明显降低。此外 ,大鼠海马各亚区内 ACh E阳性纤维面积百分比与 i NOS细胞数存在显著负相关。丹参酮 5 0 m g/ kg连续灌胃 14d后 ,分别对上述变化有不同程度的改善作用。结论　丹参酮治疗 AD样大鼠的作用机制可能与保护脑内胆碱能系统和调节Objective To investigate the therapeutic mechanism of tanshinone on learning and memory impairment induced by amyloid β-peptide 1-40 (Aβ 1-40) in rats. Methods 10 μg Aβ 1-40 was injected bilaterally into the dorsal lateral of the dentate gyrus in the hippocampus of rats. The activity of acetylcholinesterase (AChE) of each subfield in hippocampus of rats was determined by AChE histochemical technique; Immunohistochemistry was used to detect the expression of neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS) in hippocampus of rats. Results The level of AChE positive fibers of each subfield in hippocampus after Aβ 1-40 hippocampal injection in rats decreased as compared with that in control group. Immunohistochemistry showed that the expression of nNOS in model animals was downregulated, whereas the iNOS was upregulated . With tanshinone administration (50 mg/kg, ig, 14 days), the changes mentioned above could be improved to varying degrees respectively. Furthermore, the percentage of AChE positive fiber area in each subfield hippocampus was remarkably negatively correlated with the iNOS positive cells. Conclusion The mechanism that tanshinone improved the impaired learning and memory induced by Aβ 1-40 in rats might be contributed to the modulation of the activity of AChE and NOS in hippocampus

关 键 词：丹参酮 Β-淀粉样肽 胆碱能系统 一氧化氮合酶 海马 

分 类 号：R284.1[医药卫生—中药学]