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1. 重庆医科大学人体解剖教研室
2. 成都大学医学院
3. 成都市第五人民医院神经内科
纸质出版日期:2020
移动端阅览
王依滢, 高蒙, 邱国平, 等. 电针对阿尔茨海默病大鼠海马P35/P25-细胞周期素依赖性蛋白激酶5-Tau蛋白信号通路的影响[J]. 针刺研究, 2020,45(3):194-201.
WANG Yi-ying, GAO Meng, QIU Guo-ping, et al. Effect of electroacupuncture on the P35/P25-cyclin-dependent kinase 5-Tau pathway in hippocampus of rats with Alzheimer’s disease[J]. Acupuncture research, 2020, 45(3): 194-201.
王依滢, 高蒙, 邱国平, 等. 电针对阿尔茨海默病大鼠海马P35/P25-细胞周期素依赖性蛋白激酶5-Tau蛋白信号通路的影响[J]. 针刺研究, 2020,45(3):194-201. DOI: 10.13702/j.1000-0607.190415.
WANG Yi-ying, GAO Meng, QIU Guo-ping, et al. Effect of electroacupuncture on the P35/P25-cyclin-dependent kinase 5-Tau pathway in hippocampus of rats with Alzheimer’s disease[J]. Acupuncture research, 2020, 45(3): 194-201. DOI: 10.13702/j.1000-0607.190415.
目的:通过观察电针对阿尔茨海默病(AD)大鼠P35/P25-细胞周期素依赖性蛋白激酶5(CDK5)-Tau蛋白信号通路的影响
探讨电针防治AD的机制。方法:SD大鼠随机分为对照组、假手术组、模型组和治疗组
每组12只。采用双侧海马注射Aβ_(25-35)复制AD大鼠模型。治疗组电针"百会"和双侧"肾俞"穴
每次15 min
每日1次
共10 d。用Morris水迷宫检测各组大鼠学习记忆能力
免疫组织化学法检测海马组织P35/P25、CDK5、Tau5蛋白分布及表达情况
Western blot法检测上述蛋白及Tau蛋白Ser199和Ser202位点的磷酸化表达水平。结果:在可视平台实验中
各组大鼠平均逃避潜伏期与搜索路径差异均无统计学意义(P>0.05)。在隐蔽平台实验中
与对照组比较
假手术组大鼠平均逃避潜伏期和搜索路径差异均无统计学意义(P>0.05);模型组平均逃避潜伏期和搜索路径较对照组、假手术组明显延长(P<0.05);与模型组比较
治疗组平均逃避潜伏期和搜索路径明显缩短(P<0.05)。在空间探索实验中
与对照组比较
假手术组穿越原平台次数差异无统计学意义(P>0.05);模型组穿越原平台的次数较对照组和假手术组显著减少(P<0.01
P<0.05);与模型组比较
治疗组穿越原平台次数显著增加(P<0.05)。与对照组及假手术组比较
模型组P35/P25、CDK5蛋白表达均明显升高(P<0.001);治疗组P35/P25、CDK5蛋白表达较模型组明显降低(P<0.001)。各组间Tau5蛋白表达差异无统计学意义(P>0.05)。Western blot法和免疫组织化学法的结果趋势一致。模型组大鼠海马区Tau蛋白Ser199和Ser202位点的磷酸化表达水平明显高于对照组和假手术组(P<0.01
P<0.05);治疗组Tau蛋白Ser199和Ser202位点的磷酸化表达水平较模型组明显降低(P<0.05
P<0.01)。结论:电针刺激可能通过影响大鼠海马区P35/P25-CDK5-Tau信号通路相关蛋白的表达变化
从而延缓AD的进展。
Objective To investigate the effect of electroacupuncture on the P35/P25-cyclin-dependent kinase 5(CDK5)-Tau pathway in rats with Alzheimer's disease(AD)
as well as the mechanism of electroacupuncture in the prevention and treatment of AD. Methods Sprague-Dawley rats were randomly divided into control group
sham-operation group
model group
and electroacupuncture treatment group
with 12 rats in each group. A rat model of AD was established by injection of Aβ_(25-35) into the bilateral hippocampus. The rats in the electroacupuncture treatment group were given electroacupuncture at "Baihui"(GV20) and "Shenshu"(BL23) once a day
15 min each time
for 10 days. Morris water maze was used to evaluate learning and memory abilities
immunohistochemistry was used to measure the distribution and expression of P35/P25
CDK5
and Tau5 in the hippocampus
and Western blot was used to measure the expression of the above mentioned proteins
phosphory-lated Tau(Ser199
Ser202). Results In the visual platform test
there were no significant differences in escape latency and search path between groups(P>0.05). In the hidden platform test
there were no significant differences in escape latency and search path between the control group and the sham-operation group(P>0.05); the model group had significantly longer escape latency and search path than the control group and the sham-operation group(P<0.05). Compared with the model group
the electroacupuncture treatment group had significantly shorter escape latency and search path(P<0.05). In the spatial exploration test
there was no significant difference in the number of platform crossings between the control group and the sham-operation group(P<0.05). The model group had a significantly lower number of platform crossings than the control group and the sham-operation group(P<0.01
P<0.05). The electroacupuncture treatment group had a significantly higher number of platform crossings than the model group(P<0.05). Compared with the control group and the sham-operation group
the model group had significant increases in the protein expression of P35/P25 and CDK5(P<0.001)
and the electroacupuncture treatment group had significant reductions compared with the model group(P<0.001). There was no significant difference in the protein expression of Tau5 between groups(P>0.05). The model group had significantly higher protein expression of phosphorylated Tau(Ser199
Ser202) in the hippocampus than the control group and the sham-operation group(P<0.01
P<0.05). The electroacupuncture treatment group had significantly lower protein expression of phosphorylated Tau(Ser199
Ser202) than the model group(P<0.05
P<0.01). Conclusion Electroacupuncture may delay the progression of AD by affecting the expression of proteins involved in the P35/P25-CDK5-Tau pathway in the hippocampus of rats.
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