五脏温阳化瘀汤抑制周期蛋白依赖激酶-5过表达对SAMP8小鼠脑神经纤维缠结的影响  

Effect of Wuzang Wenyang Huayu Decoction on Neurofibrillary Tangles by Inhibiting Cyclin-dependent Kinase-5 Over-expression in SAMP8 Mice

作　　者：农微[1] 卫智权[1] 莫雪妮[1] 吴林[1] 唐农[1] NONG Wei;WEI Zhi-quan;MO Xue-ni;WU Lin;TANG Nong(Guangxi Key Laboratory of Chinese Medicine Foundation Research,Guangxi University of Chinese Medicine, Nanning 530001,China)

机构地区：[1]广西中医药大学广西中医基础研究重点实验室,南宁530001

出　　处：《中国实验方剂学杂志》2019年第9期61-66,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81573938);广西中医基础研究重点实验室开放课题项目(16-380-58-09;K201137907;K201137909)

摘　　要：目的:探讨五脏温阳化瘀汤改善SAMP8小鼠认知能力的周期蛋白依赖性激酶-5(CDK-5)相关脑神经纤维缠结机制。方法:10只SAMR1小鼠为正常组,40只SAMP8小鼠随机分为模型组,多奈哌齐组(0.4 mg·kg^(-1)·d^(-1)),五脏温阳化瘀汤高、低剂量组(5,1.25 g·kg^(-1)·d^(-1)),连续灌胃给药4周。Morris水迷宫测试定位航行与空间探索能力;实时荧光定量聚合酶链式反应(Real-time PCR)检测脑神经组织CDK-5 mRNA表达水平;蛋白免疫印迹法(Western blot)检测脑神经组织CDK-5蛋白表达与Tau蛋白磷酸化水平;银染法检测脑神经纤维缠结。结果:与正常组比较,模型组脑神经组织CDK-5与Tau蛋白磷酸化表达水平均显著升高(P<0.01),脑神经纤维缠结明显增多,定位航行与空间探索能力显著减弱(P<0.01);与模型组比较,五脏温阳化瘀汤高、低剂量组脑神经组织CDK-5与Tau蛋白磷酸化表达水平均明显降低(P<0.05,P<0.01),脑神经纤维缠结减少,小鼠定位航行并空间探索能力明显改善(P<0.05,P<0.01)。结论:五脏温阳化瘀汤可显著改善SAMP8小鼠认知能力,可能与其抑制CDK-5过表达进而抑制Tau蛋白过磷酸化导致脑神经纤维缠结减少有关。Objective: To explore the mechanism of Wuzang Wenyang Huayu decoction in improving the cognitive competence and the pharmacological mechanism for neurofibrillary tangles related to cyclin-dependent kinase-5( CDK-5). Method: The 10 SAMR1 mice were used as normal group,40 SAMP8 mice were randomly divided into model group,donepezil group( 0. 4 mg·kg^-1·d^-1),high and low dose Wuzang Wenyang Huayu decoction groups( 5,1. 25 g·kg^-1·d^-1). Drugs were administered by gastric lavage for 4 continuous weeks.Directional navigation and space exploration ability were evaluated with Morris amaze. Real-time PCR was used to measure the mRNA expression of CDK-5 in brain nerve tissues. Western blot was used to detect the protein expression of CDK-5 and phosphorylation of Tau protein. Meanwhile,neurofibrillary tangles in brain tissue were detected with silver staining method. Result: As compared with normal group,both CDK-5 expression and Tau protein phosphorylation in brain nerve tissues were remarkably increased in model group( P< 0. 01),with significantly increased neurofibrillary tangles and significantly decreased directional navigation ability and space exploration ability( P< 0. 01). As compared with model group,CDK-5 expression and Tau protein phosphorylation were lower in Wuzang Wenyang Huayu decoction treated groups( P <0. 05, P< 0. 01),accompanied by decreased number of neurofibrillary tangles as well as improved directional navigation and space exploration ability( P <0. 05,P< 0. 01). Conclusion: Wuzang Wenyang Huayu decoction can markedly improve the cognitive competence of SAMP8 mice,and the mechanism may be related to its inhibition on CDK-5 over-expression,and down-regulation of Tau protein phosphorylation and neurofibrillary tangles in brain tissue.

关 键 词：五脏温阳化瘀汤 桂枝加附子汤 痴呆 周期蛋白依赖性激酶-5 (CDK-5) Tau蛋白过磷酸化 神经纤维缠结 

分 类 号：R289[医药卫生—方剂学] R745.1[医药卫生—中药学]