Fan Jun-Chao, Song Jun-Jie, Wang Ying, Chen Ying, Hong Dao-Xian
Department of Anesthesiology, First Affiliated Hospital of Henan University, Kaifeng, Henan, 475000, China.
Department of Anesthesiology, First Affiliated Hospital of Henan University, Kaifeng, Henan, 475000, China.
Asian Pac J Trop Med. 2017 Oct;10(10):1007-1010. doi: 10.1016/j.apjtm.2017.09.014. Epub 2017 Sep 18.
To discuss the neuron-protective effect and possible mechanism of subanesthestic-dosage ketamine on Parkinson's disease mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
A total of 30 mice were divided equally into three groups, model control group (MC group), ketamine treatment group (KT group), and blank control group (BC group), respectively. The Parkinson's disease mice of MC group and KT groups were established by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (20 mg/kg/d), while mice in KT group were treated by intraperitoneal injection of subanesthestic-dosage ketamine (8 mg/kg). Differences on behaviors and the number of nigra dopaminergic neurons of mice in each group were compared through the behavioral test and tyrosine hydroxylase immunohistochemistry experiments after the treatments. Furthermore, Western blot was used to test the expression of autophagy-related gene LC3-Ⅱ, Beclin1, Parkin, PINK1, and mTOR.
Compared with the BC group, the neuroethology scores were lower and the amount of TH positive cells were less both in MC and MT groups; In KT group, the neuroethology scores were higher and the amount of tyrosine hydroxylase positive cells were significantly more than that in MC group (P < 0.05). Moreover, expression levels of autophagy-related proteins LC3-II, Beclin1, Parkin, and PINK1 were higher, while the mTOR expression level was lower than that in MC group.
The subanesthestic-dosage ketamine has some protective effects on the coordinating ability of movement and cognitive ability of Parkinson's disease mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. This is probably due to that the autophagy activity of cells is activated by subanesthestic-dosage ketamine and that the neurons are protected.
探讨亚麻醉剂量氯胺酮对1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的帕金森病小鼠的神经保护作用及可能机制。
将30只小鼠平均分为三组,分别为模型对照组(MC组)、氯胺酮治疗组(KT组)和空白对照组(BC组)。MC组和KT组的帕金森病小鼠通过腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(20mg/kg/d)建立模型,而KT组小鼠则通过腹腔注射亚麻醉剂量氯胺酮(8mg/kg)进行治疗。治疗后,通过行为学测试和酪氨酸羟化酶免疫组化实验比较各组小鼠的行为和黑质多巴胺能神经元数量的差异。此外,采用蛋白质免疫印迹法检测自噬相关基因LC3-Ⅱ、Beclin1、Parkin、PINK1和mTOR的表达。
与BC组相比,MC组和MT组的神经行为学评分较低,TH阳性细胞数量较少;KT组的神经行为学评分较高,酪氨酸羟化酶阳性细胞数量明显多于MC组(P<0.05)。此外,自噬相关蛋白LC3-II、Beclin1、Parkin和PINK1的表达水平较高,而mTOR表达水平低于MC组。
亚麻醉剂量氯胺酮对1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的帕金森病小鼠的运动协调能力和认知能力具有一定的保护作用。这可能是由于亚麻醉剂量氯胺酮激活了细胞的自噬活性,从而保护了神经元。