天泰1号对自发老年性痴呆模型中枢胆碱能系统活性的影响

背景:天泰1号由天麻、当归、槟榔等组成,具有补肝养髓和益智开窍的功能。目的:观察天泰1号对自发老年性痴呆模型学习记忆功能及中枢胆碱能活性的影响。设计:随机对照观察。单位:深圳市中西医结合研究所。材料:选取昆明种雄性小鼠,13个月龄,饲养至21个月龄,筛选自发老年性痴呆鼠52只。随机分为空白对照组、西药对照组、天泰1号6.80g/kg组、天泰1号20.41g/kg组4组。同期选取13只筛选出的老年学习记忆正常鼠做正常对照组。方法:西药对照组给以Hydergine0.6mg/kg,天泰1号6.80g/kg组和20.41g/kg组分别予天泰1号6.80g/kg及20.41g/kg,连续60d,正常对照和空白对照组均灌以等量双蒸馏水。采用跳台实验检测学习记忆成绩鸦脑组织冰冻切片,Hedreen法示胆碱酯酶纤维,Burt及Silver法示胆碱乙酰转移酶,全自动显微图像分析系统定量检测相关脑区胆碱酯酶纤维及胆碱乙酰转移酶活性。主要观察指标:①观察天泰1号对老年性痴呆大鼠学习记忆的影响。②观察颞叶皮质和海马CA1区的胆碱酯酶阳性纤维面密度。③观察基底前脑Meynert核区胆碱乙酰转移酶活性。结果:①天泰1号对自发性老年痴呆鼠学习记忆的改善作用:天泰1号6.80g/kg组、天泰1号20.41g/kg组、正常对照组和西药对照组的错误次数显著低于空白对照组(5.08±2.18,3.77±1.48,3.25±1.27,6.17±3.12,9.31±3.65,P<0.05)。②胆碱酯酶阳性纤维面密度:在颞叶皮质区,天泰1号6.80g/kg组、天泰1号20.41g/kg组、正常对照组和西药对照组显著高于空白对照组(20.19±4.18,25.01±6.44,26.38±6.52,19.44±4.33,14.36±3.21,P<0.05)。在海马CA1区,天泰1号20.41g/kg组和正常对照组显著高于空白对照组、西药对照组和天泰1号6.80g/kg组(13.88±3.07,14.11±4.36,6.57±2.30,10.13±2.94,9.63±2.40,P<0.05)。③神经元胆碱乙酰转移酶活性:天泰1号20.41g/kg组、天泰1号6.80g/kg组、西药对照组和正常对照组显著高于空白对照组(0.683±0.179,0.589±0.179,0.552±0.173,0.705±0.141,0.354±0.131,P<0.05)。结论:天泰1号可明显改善自发老年性痴呆模型的学习记忆障碍,显著增强其中枢胆碱能系统活性,且呈现明显的量效关系。

Effects of Tiantai Ⅰ on the activity of central cholinergic system in mice with spontaneous Alzheimer disease

BACKGROUND: Tiantai I consists of gastrodia, Chinese angelica root, areca seed. It has been considered as the roles of invigorating the liver, nourishing marrow, heightening the intelligence and causing resuscitation. OBJECTIVE: To observe the effects of Tiantai Ⅰ on the abilities of learn ing and memory and the activity of central cholinergic system in mice with spontaneous Alzheimer disease. DESIGN: A randomized control observation. SETTING: Shenzhen Institute of Integrated Chinese and Western Medicine. MATERIALS: Male Kunming mice of 13 months old were raised to 21 months old, of which 52 with spontaneous Alzheimer disease were screened. They were randomly divided into blank control group, western drug control group, Tiantai Ⅰ 6.80 and 20.41 g/kg groups, 13 mice in each group. Another 13 aged mice with normal learning and memory abilities were selected as the normal control group at the same time. METHODS: Mice in the western drug control group were treated with 0.6 mg/Kg Hydergine, those in the Tiantai Ⅰ 6.80 and 20.41 g/kg groups were given intragastric administration of Tiantai Ⅰ of 6.80 and 20.41 g/kg, respectively, and those in the normal control group and blank control group were given double distilled water of the same volume. The learning and memory results were examined by the step-down test. Freezing sections of brain tissue were prepared, acetylcholinesterase (AChE) fiber was showed according to the Hedreen method, and choline acetyltransferase (ChAT) was detected with Burt and Silver methods, the automatic image analysis system for biomedical application was applied in the quantitative analysis of AChE fiber and ChAT activity. MAIN OUTCOME MEASURES: ① Effect of Tiantai Ⅰ on the abilities of learning and memory in mice with Alzheimer disease; ② AChE fiber area density in temporal cortex and hippocampal CA1 region; ③ ChAT ac tivity in Meynert nuclei of basal forebrain. RESULTS: ① Tiantai Ⅰ in ameliorating the abilities of learning and mem ory in mice with spontaneous Alzheimer disease: The error times in the Tiantai Ⅰ 6.80 and 20.41 g/kg groups, normal control group and western drug control group were obviously fewer than that in the blank control group (5.08±2.18, 3.77±1.48, 3.25±1.27, 6.17±3.12, 9.31±3.65, P ＜ 0.05). ② AChE fiber area density: The AChE fiber area densities in temporal cortex were obviously higher in the Tiantai Ⅰ 6.80 and 20.41 g/kg groups, normal control group and western drug control group than in the blank control group (20.19±4.18, 25.01±6.44, 26.38±6.52, 19.44±4.33, 14.36±3.21, P ＜ 0.05). The AChE fiber area densities in hippocampal CA1 region were obviously higher in the Tiantai Ⅰ 20.41 g/kg groups and nor mal control group than in the blank control group, western drug control group and Tiantai Ⅰ 6.80 g/kg group (13.88±3.07, 14.11±4.36, 6.57±2.30, 10.13±2.94, 9.63±2.40, P ＜ 0.05). ③ ChAT activity: It was obviously high er in the TiantaiI 20.41 and 6.80 g/kg groups, western drug control group and normal control group than in the blank control group (0.683±0.179, 0.589±0.179, 0.552±0.173, 0.705±0.141, 0.354±0.131, P ＜ 0.05). CONCLUSION: Tiantai Ⅰ can significantly improve the disturbances of learning and memory in mice with spontaneous Alzheimer disease, and it can increase the activity of central cholinergic system in a dose-dependent manner.