补肾化痰法对Alzheimer′s病模型大鼠脑组织Gsk-3β活性的影响及作用机制  

The Effect and Potential Mechanism of Replenishing Kidney-essence Removing Phlegm Therapy on GSK-3β on Hyperphos-phorylation for AD Rat Model

作　　者：胡慧[1] 王平[1] 孔明望[1] 丁凤敏[1] 

机构地区：[1]湖北中医学院,湖北武汉430061

出　　处：《中华中医药学刊》2009年第9期1845-1847,共3页Chinese Archives of Traditional Chinese Medicine

基　　金：国家中医药管理局基金资助项目(04-05JP41);湖北省卫生厅科研基金资助项目(JX2B66)

摘　　要：目的:观察补肾化痰法对AD模型大鼠GSK-3β活性的影响并探讨其可能机制。方法:应用脑立体定向技术给大鼠BNM注射凝聚态Aβ25-35+IBO构建AD模型。注射2周后,高、中、低量组分别给大鼠该药水煎液灌胃;西药组用哈伯因混悬液灌胃;正常组、空白组、模型组均给予等容积的生理盐水灌胃。28天后采用酶联免疫吸附法检测大鼠脑组织GSK-3β活性。结果:模型组GSK-3β的表达较正常组均有显著性的提高(P<0.01)。给药后发现不但大鼠海马组织Tau蛋白异常磷酸化水平下降,高、中量组与模型组比较显著降低(P<0.01),与西药组也有差异(P<0.01);而且GSK-3β的表达亦明显低于模型组,尤以高量组的作用最明显,高、中、低量组存在一定量效关系(P<0.01)。结论:补肾化痰法可以可能通过抑制GSK-3β的活性,降低Tau蛋白异常磷酸化水平,从而发挥其抗老年性痴呆的作用。Objective：To establish the AD rat model induced by injection of basal nucleus of Meynert（BNM） with ibotenic acid（IBO） and 25-35 β-amyloid peptide（Aβ 25-35）.And to explore the effect and potential mechanism of replenishing kidney-essence,removing phlegm therapy on GSK-3β on hyperphos-phorylation for AD.Methods：To induce AD,five groups rats received injection of IBO and Aβ 25-35 with basal nucleus of Meynert（BNM） through stereospeetific instrument.After treating for two weeks,BuShen HuaTan decoction were administered by oral gavage for the three doses groups. Huperzine A - Zhulin Antun tablets served as control drug. Normal group, model group and blank group were administered by isovolumetric saline water. After treating for four weeks, enzyme linked immunosorbent assay was used to glycogen synthase kinase 3β（ GSK - 313）, to observe their effects on the above marks. Results ：The expression of GSK- 3β in model group have marked increased than normal group（ P 〈 0. 01 ）. After administrated by BSHT decoction, not noly the total level of phosphorylation tau protein, but also the expression of GSK - 3β have remarkedly increased, especially the high -treated group. Moreover,the high -treated, middle - treated and lowtreated groups have dose -effect relationship （ P 〈 0.01 ）. Conclusion： Replenishing kidney -essence and removing phlegm therapy can inhibit the activity of GSK - 3β and decrease the level of tau protein hyper - pbosphorylation.

关 键 词：补肾化痰法 ALZHEIMER 糖元合成酶激酶3β(GSK-3β) TAU蛋白 

分 类 号：R-33[医药卫生]