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[1]吕润潇,杜莉莉,周凤华,等.迷迭香酸抑制PI3K/Akt/mTOR信号通路促进细胞自噬 缓解帕金森的机制研究[J].宁夏医科大学学报,2019,(12):1189-1194.[doi:10.16050/j.cnki.issn1674-6309.2019.12.001]
 LYU Runxiao,DU Lili,ZHOU Fenghua,et al.Mechanism of Rosmarinic Acid Inhibiting PI3K/Akt/mTOR Signaling Pathway and Promoting Autophagy to Alleviate Parkinson's Disease[J].Ningxia Medical University,2019,(12):1189-1194.[doi:10.16050/j.cnki.issn1674-6309.2019.12.001]
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迷迭香酸抑制PI3K/Akt/mTOR信号通路促进细胞自噬 缓解帕金森的机制研究(PDF)
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《宁夏医科大学学报》[ISSN:1005-8486/CN:64-1029/R]

卷:
期数:
2019年12期
页码:
1189-1194
栏目:
论著
出版日期:
2020-03-27

文章信息/Info

Title:
Mechanism of Rosmarinic Acid Inhibiting PI3K/Akt/mTOR Signaling Pathway and Promoting Autophagy to Alleviate Parkinson's Disease
文章编号:
1674-6309(2019)12-1189-06
作者:
吕润潇1 杜莉莉2 周凤华1 张立新1 刘学勇1
(1. 中国医科大学附属盛京医院,沈阳 110000; 2. 中国医科大学基础医学院,沈阳 110000)
Author(s):
LYU Runxiao1 DU Lili2 ZHOU Fenghua1 ZHANG Lixin1 LIU Xueyong1
(1. Shengjing Hospital of China Medical University,Shenyang 110000,China; 2. College of Basic Medical Science,China Medical University,Shenyang 110000,China)
关键词:
帕金森迷迭香酸磷脂酰肌醇3-激酶蛋白激酶B雷帕霉素靶蛋白自噬小鼠
Keywords:
parkinsonrosmarinic acidphosphatidy linositd 3-kinaseprotein dinase Bmammlian target of rapamycin autophagymouse
分类号:
R742.5
DOI:
10.16050/j.cnki.issn1674-6309.2019.12.001
文献标志码:
A
摘要:
目的 探讨迷迭香酸(RA)对1-甲基-4苯基-1,2,3,6四氢吡啶(MPTP)诱导的小鼠帕金森模型细胞自噬的调控作用及可能的分子机制。方法 30只C57BL/6小鼠随机分为对照(control)组、模型(MPTP)组、治疗低剂量(MPTP+low RA)组、治疗中剂量(MPTP+middle RA)组、治疗高剂量(MPTP+high RA)组,每组6只;小鼠连续8 d腹腔注射25 mg·kg-1 MPTP建立帕金森模型,造模后第9天,三组治疗组连续8 d分别腹腔注射1、4和16 mg·kg-1 的RA。通过爬杆实验和悬挂实验对小鼠进行行为学评分;Real-time PCR及Western blot检测各组小鼠脑组织Bcl-2和Beclin-1 mRNA及蛋白表达水平;Western blot检测各组小鼠脑组织LC3Ⅱ/Ⅰ比值及磷脂酰肌醇3-激酶(phosphatidy linositol 3-kinase,PI3K)、蛋白激酶B(protein dinase B,Akt)和哺乳动物雷帕霉素靶蛋白(mammlian target of rapamycin,mTOR)表达及磷酸化水平。结果 与control组相比,MPTP组小鼠运动协调能力下降,Bcl-2、Beclin-1 mRNA水平降低,Bcl-2、Beclin-1和LC3Ⅱ/Ⅰ蛋白表达水平降低, PI3K、Akt和mTOR蛋白磷酸化水平升高(P均<0.05);与MPTP组相比,RA治疗组提升小鼠运动协调能力,Bcl-2、Beclin-1 mRNA和蛋白水平升高,LC3Ⅱ/Ⅰ蛋白表达水平上调,PI3K、Akt和mTOR磷酸化水平下调,并且随RA治疗浓度增加变化越显著(P均<0.05)。结论 RA剂量依赖性地抑制PI3K/Akt/mTOR通路促进帕金森小鼠脑组织的细胞自噬和抑制细胞凋亡。
Abstract:
Objective To investigate the regulation of rosmarinic acid(RA)on 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine(MPTP)-induced autophagy in mouse Parkinson's model and its possible molecular mechanism. Methods C57BL/6 mice were randomly divided into control group, model group (MPTP), low-dose group (MPTP+low RA group), middle-dose group (MPTP+middle RA group), and high-dose group (MPTP +high RA group). The Parkinson models were established by intraperitoneal injection of 25 mg·kg-1 MPTP for 8 consecutive days. On the 9th day after modeling, the three treatment groups were intraperitoneally injected with 1, 4, 16 mg·kg-1 RA for 8 consecutive days. The behavioral scores of mice were evaluated by pole test and traction test. Real-time PCR and Western blot were used to detect the expression of Bcl-2 and Beclin-1 mRNA and protein in brain tissue. Western blot was used to detect the ratio of LC3II/I and the expression of PI3K, Akt and mTOR protein and phosphorylation in brain tissue of each group. Results Compared with control group, the motor coordination ability of MPTP group decreased significantly. The levels of Bcl-2 and Beclin-1 mRNA were decreased significantly, and the expression levels of Bcl-2, Beclin-1 and LC3II/I protein were decreased significantly. The phosphorylation levels of PI3K, Akt and mTOR protein were increased significantly(P<0.05). Compared with MPTP group, RA treatment group improved the motor coordination ability of mice. The levels of Bcl-2 and Beclin-1 mRNA and protein were significantly increased, and the level of LC3 II/I protein was significantly increased. The phosphorylation levels of PI3K, Akt and mTOR were decreased significantly with the increase of RA concentration(P<0.05). Conclusion RA dose-dependent inhibition of PI3K/Akt/mTOR pathway promotes autophagy and inhibits apoptosis in brain tissue of Parkinson's mice.

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备注/Memo

备注/Memo:
收稿日期:2019-02-26
基金项目:辽宁省自然科学基金计划重点项目(20180540067)
作者简介:吕润潇,男,辽宁人,博士,讲师,研究方向:骨科运动康复,脊髓损伤。
通信作者:刘学勇。E-mail:lxykfzx@163.com
更新日期/Last Update: 2019-12-30