[1]唐雪梅,蒋学华,徐露.贝沙罗汀对帕金森大鼠黑质神经元凋亡及mTOR/AKT/GSK3β通路的影响[J].第三军医大学学报,2018,40(04):328-332.
 TANG Xuemei,JIANG Xuehua,XU Lu.Protective effect of bexarotene against apoptosis of substantia nigra neurons in Parkinson rats and role of mTOR /AKT/GSK-3β pathwa[J].J Third Mil Med Univ,2018,40(04):328-332.
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贝沙罗汀对帕金森大鼠黑质神经元凋亡及mTOR/AKT/GSK3β通路的影响(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
40卷
期数:
2018年第04期
页码:
328-332
栏目:
基础医学
出版日期:
2018-02-28

文章信息/Info

Title:
Protective effect of bexarotene against apoptosis of substantia nigra neurons in Parkinson rats and role of mTOR /AKT/GSK-3β pathwa
作者:
唐雪梅蒋学华徐露
四川大学华西药学院;四川省第四人民医院药剂科;重庆医药高等专科学校
Author(s):
TANG Xuemei JIANG Xuehua XU Lu

West China School of Pharmacy, Sichuan University, Chengdu, Sichuan Province, 610041; Fourth People’s Hospital of Sichuan Province, Chengdu, Sichuan Province, 610021; Chongqing Medical and Pharmaceutical College, Chongqing, 401331, China

关键词:
贝沙罗汀&alpha-SYNAKTGSK-3&betamTOR
Keywords:
bexarotene &alpha-synuclein mammalian target of rapamycin AKT glycogen synthase kinase-3&beta
分类号:
R742.5;R969;R971.5
文献标志码:
A
摘要:

目的    探讨贝沙罗汀对6羟多巴胺诱导的帕金森大鼠黑质神经元凋亡及mTOR/AKT/GSK3β通路的影响。方法    选取50只健康雄性SD大鼠,按随机数字表法分为假手术组,帕金森模型组,贝沙罗汀高、中、低剂量组(分别为100、50、25 mg/kg,1次/d,连续4周),每组10只。向帕金森模型组及贝沙罗汀高、中、低剂量组大鼠的右侧大脑纹状体注射6-羟多巴胺,建立帕金森大鼠模型;假手术组仅注射生理盐水。观察大鼠转圈数、速度和左前肢使用率;TUNEL染色法检测黑质神经元凋亡情况;免疫组化法检测黑质部位α-SYN的表达;Western blot检测黑质部位mTOR、p-mTOR(Ser2448)、AKT、p-AKT(Ser473)、GSK-3β和p-GSK-3β(Ser9)蛋白的表达。结果   与模型组相比,贝沙罗汀高、中、低剂量组旋转圈数、转速显著降低,左前肢使用率显著升高(P<0.01),凋亡神经元数量显著减少(P<0.01),黑质部位α-SYN的表达显著降低(P<0.01),mTOR、p-mTOR、AKT、pAKT、GSK-3β和p-GSK-3β的表达明显上调(P<0.01)。结论    贝沙罗汀对6羟多巴胺诱导的帕金森大鼠的黑质神经元具有显著的抑制凋亡作用,其机制可能与激活mTOR/ AKT/GSK3β信号通路有关。

Abstract:

Objective    To investigate the protective effect of bexarotene against apoptosis of substantia nigra neurons in a rat model of 6-hydroxydopamine (6-OHDA)-induced Parkinson’s disease (PD) and explore the role of mTOR/AKT/GSK-3β pathway in mediating this effect. Methods    Fifty healthy male SD rats were randomized into control group, PD model group, and high-, medium- and low-dose bexarotene treatment groups. Rat models of PD were established in the model group and the 3 bexarotene treatment groups by injecting 6-OHDA into the right striatum; the rats in the control group received an injection with saline only. One day after 6-OHDA injection, the rats in high-, medium- and low-dose bexarotene group were subjected to intragastric administration of 100, 50, and 25 mg/kg bexarotene, respectively, once daily for 4 consecutive weeks. The rats were observed for the number of rotations, rotating speed and left forelimb usage; neuronal apoptosis was detected with TUNEL assay, and immunohistochemistry was performed to detect the expression of α-SYN in the substantia nigra. Western blotting was used to detect the expression levels of mTOR, pmTOR (Ser2448), AKT, p-AKT (Ser473), GSK-3β and p-GSK-3β (Ser9) in the substantia nigra. Results    Compared with those in the model group, the rats in high-, medium- and low-dose bexarotene groups showed significantly reduced number of rotations, lowered rotating speed, and significantly increased left forelimb usage (P<0.01). Bexarotene treatment significantly reduced neuronal apoptosis, decreased α-SYN expression (P<0.01), and lowered the expression of mTOR, p-mTOR, AKT, p-AKT, GSK-3β and p-GSK-3β proteins (P<0.01) in the substantia nigra of the Parkinsonian rats. Conclusion    Bexarotene can reduce neuronal apoptosis in the substantia nigra of rats with 6-OHDAinduced PD, the mechanism of which may involve the activation of mTOR/AKT/GSK-3β signaling pathway.

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更新日期/Last Update: 2018-03-03