五脏温阳化瘀汤对SAMP8小鼠Tau蛋白过磷酸化与神经纤维缠结的抑制作用

Inhibition of Wuzang Wenyang Huayu Decoction on Tau Protein Over-Phosphorylation and Neurofibrillary Tangles in SAMP8 Mice

目的:探讨五脏温阳化瘀汤对SAMP8小鼠神经组织Tau蛋白过磷酸化与神经纤维缠结的抑制作用。方法:50只SAMP8小鼠随机分为正常对照组、模型对照组、多奈哌齐组(0.4 mg·kg-1·d-1)与五脏温阳化瘀汤高、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,WB检测神经组织Tau蛋白磷酸化水平与蛋白激酶A(PKA)催化亚基,银染法检测神经组织神经纤维缠结,透射电子显微镜观察神经纤维微管超微结构。结果:五脏温阳化瘀汤显著降低PKA催化亚基水平,抑制Tau蛋白过磷酸化与神经纤维缠结,维持神经纤维微管超微结构完整,缩短小鼠定位航行潜伏期并改善空间探索能力。结论:五脏温阳化瘀汤改善认知能力可能与其减少PKA催化亚基从而抑制Tau蛋白过磷酸化、神经纤维缠结有关。

Objective:To investigate the inhibition of Wuzang Wenyang Huayu Decoction on Tau protein over-phosphorylation and neurofibrillary tangles in SAMP8 mice.Methods:Fifty SAMP8 mice were randomly divided into normal control,model control,donepezil(0.4 mg·kg-1·d-1)and Wuzang Wenyang Huayu Decoction high and low dosegroups(5,1.25 g·kg-1·d-1).Drugs were administered by gastric lavage for 4 weeks.Directional navigation and space exploration ability were measured with Morris amaze.Western blotting was executed to analyze protein kinase A(PKA)catalytic subunit and Tau protein phosphorylation in nerve tissue.Neurofibrillary tangles(NFT)were detected with silver staining.Neurofibrillary microtubule ultrastructure was probed in a transmission electron microscope.Results:Wuzang Wenyang Huayu Decoction reduced PKA catalytic subunit and inhibited phosphorylation of Tau protein,accompanied by shortening the directional navigation latency and improving the space exploration ability and maintaining the neurofibrillary microtubule ultrastructure integrity.Conclusion:The improved cognitive competence by Wuzang Wenyang Huayu Decoction might be related to its inhibition on Tau protein over-phosphorylation and NFT through reducting PKA catalytic subunit.