基于CaMkkβ/AMPK通路介导线粒体自噬探讨敛肝熄风止颤方的神经保护机制  

Study on the Neuroprotective Mechanism of Lianggan Xifeng Zhichan Formula Based on Mitochondrial Autophagy Mediated by CaMkkβ/AMPK Pathway

作　　者：王春玲 罗宁 蒋媛静[2] 蒙冰[2] 左曜玮 李昌海 文晓东[2] WANG Chunling;LUO Ning;JIANG Yuanjing;MENG Bing;ZUO Yaowei;LI Changhai;WEN Xiaodong(College of Pharmacy,Guangxi University of Traditional Chinese Medicine,Nanning 530001,China;Department of Neurology,Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine,Nanning 530011,China)

机构地区：[1]广西中医药大学药学院,南宁530001 [2]广西中医药大学附属瑞康医院神经内科,南宁530011

出　　处：《世界中医药》2021年第5期765-768,774,共5页World Chinese Medicine

基　　金：广西卫生厅立项项目(Z2016220);广西中医药大学2018年广西一流学科建设项目重点课题(2018XK089)。

摘　　要：目的:观察敛肝熄风止颤方对帕金森病(Parkinson Disease,PD)的影响,探讨其神经保护机制。方法:将60只SD大鼠分为假手术组10只,造模组50只,造模组大鼠接受PD模型制备,将成模的40只大鼠随机分为模型组10只、低剂量组(0.36 g/kg)10只、中剂量组(0.72 g/kg)及高剂量组(1.44 g/kg)10只,持续灌胃给药30 d,比较各组大鼠阿扑吗啡诱导旋转次数、圆筒实验,纹状体超微结构以及CaMkkβ、AMPK、p-AMPK水平的变化。结果:1)敛肝熄风止颤方可明显减少大鼠转圈以及肢体碰壁的次数,随着剂量增加次数减少更明显,差异有统计学意义(P<0.05)。2)造模大鼠纹状体线粒体自噬现象减弱,敛肝熄风止颤方可明显促进脑组织线粒体自噬。3)中药干预后大鼠纹状体CaMkkβ、p-AMPK蛋白表达上调,与模型组比较,差异有统计学意义(P<0.05),其中高剂量组较低剂量组上调明显,差异有统计学意义(P<0.05)。结论:敛肝熄风止颤方对帕金森病具有神经保护作用,其机制之一可能是通过激活CaMkk/AMPK通路活性促进线粒体自噬有关。Objective:To observe the effect of Lianggan Xifeng Zhichan Formula(LGXFZC)on Parkinson′s disease(Parkinson′s disease,PD)and explore its neuroprotective mechanism.Methods:A total of 60 SD rats were divided into a sham operation group(n=10)and a model group(n=50).The rats in the model group were made by PD model.40 rats were randomly divided into a model group(n=10),a low dose group(0.36 g/kg)(n=10),a middle dose group(0.72 g/kg)and a high dose group(1.44 g/kg)for 30 days.The rotation times of apomorphine,cylinder test,ultrastructure of striatum and the levels of CaMkkβ,AMPK and p-AMPK were compared in each group.Results:1)LGXFZC could significantly reduce the frequency of rotation and limb touching wall in rats.As the dose increases,the frequency decreases more obviously.The difference was statistically significant(P<0.05).2)the phenomenon of mitochondrial autophagy in striatum of model rats was weakened,and LGXFZC could obviously promote mitochondrial autophagy in brain tissue.3)after the intervention of Chinese medicine,the expression of CaMkkβand p-AMPK protein in the striatum of rats was significantly higher than that in the model group(P<0.05),and compared with the model group,the difference is statistically significant(P<0.05).Among them,the high-dose group and the lower-dose group were up-regulated significantly(P<0.05).Conclusion:LGXFZC has neuroprotective effect,and one of its mechanisms may be that it promotes mitochondrial autophagy by activating the activity of CaMkk/AMPK pathway.

关 键 词：帕金森病 敛肝熄风止颤方 机制 线粒体 自噬 神经保护 CaMkkβ/AMPK通路 

分 类 号：R289.5[医药卫生—方剂学] R741[医药卫生—中药学]