摘要
目的研究温脾通络开窍汤对AD大鼠海马糖原合酶激酶-3β(GSK-3β)和蛋白质磷酸酶2A(PP2A)活性的影响,并探讨其可能的机制。方法运用脑立体定位技术向大鼠右侧海马注射冈田酸,制备老年性痴呆大鼠动物模型,造模14d后,采用经典的Morris水迷宫进行老年性痴呆大鼠模型的筛选,将造模成功大鼠随机分为模型组,西药组,温脾通络开窍汤高、中、低剂量组,另设空白组。于造模后第20天开始治疗,各治疗组给予相应的药物灌胃,模型组及空白组给予等体积的双蒸水灌胃。26d后,通过酶联免疫吸附法检测PP2A和GSK-3β的活性。结果模型组GSK-3β的活性较空白组均有提高(P<0.05),而PP2A表达两者相比有显著性降低(P<0.05)。中药高、中剂量组与模型组相比,GSK-3β的活性明显低于模型组(P<0.05),而PP2A的表达明显高于模型组(P<0.05),其中尤以中药高剂量组作用最明显,中药高、中、低剂量组存在一定量效关系。结论温脾通络开窍汤治疗老年性痴呆的可能机制是抑制GSK-3β的活性和提高PP2A的活性,从而降低tau蛋白异常磷酸化水平达到抗AD的作用。
Objective To investigate the influence and the possible mechanism of Wenpi Tongluo Kaiqiao decoction（WTKD） on the activity of protein phosphatase 2A（PP2A） and glycogen synthase kinase - 3β（GSK - 3β） in hippocampus of rats with Alzheimer disease（AD）. Methods The AD rat models were established by injecting okadaic acid into the right hippocampus with the brain ster- eotaxic technique. After 14 days, the AD rat models were screened by the classic Morris water maze,and divided randomly into model group,western medicine group,WTKD high dosage, middle dosage and low dosage treatment groups, and control group. The treat- ment began after 20 days of model establishment,and every treatment group was supplied with intragastric medicine, and the model group and control group are supplied with intragastric double distilled water. After treatment of 26 days, the activity of PP2A and GSK - 3β were detected with the enzyme linked immunosorbent assay. Results The activity of GSK - 3β in the model group was higher than that in the control group（P〈0.05）. The expression of PP2A was lower than before in two groups（P〈0.05）. The activity of GSK - 3β in WTKD high dosage and middle dosage treatment groups group were lower than that in the model group（P〈0.05）. The expression of PP2A in WTKD high dosage and middle dosage treatment groups group were higher than that in the model group（P〈 0.05）. The WTKD high dosage treatment group had the most obvious effect. There was a certain dose--effect relationship in WTKD treatment groups. Conclusion WTKD had the role of anti - AD,which could inhibit activity of GSK - 3βand improve the activity of PP2A,thereby decrease Tau protein abnormal phosphorylation level in AD.
出处
《中西医结合心脑血管病杂志》
2013年第5期581-583,共3页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
广西中医学院中药药效研究重点实验室开放基金课题(No:09-007-06-06)
广西高等学校优秀人才资助计划基金项目
作者简介
杨进平，现为广西中医药大学2010级硕士研究生（邮编：530001）；
吴林（通讯作者）
