摘要
目的:评价丙泊酚对帕金森病(PD)小鼠多巴胺能神经元的影响。方法:清洁级健康雄性C57BL/6小鼠48只,8~12周龄,体重22~32 g,采用随机数字表法分为3组(n=16):对照组(C组)、PD组和丙泊酚组(Pro组)。PD组和Pro组腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶,C组腹腔注射等容量生理盐水,连续7 d;每天腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶后30 min时,Pro组腹腔注射丙泊酚25 mg/kg,C组和PD组腹腔注射等容量生理盐水。造模结束后第8天时进行步距实验和转棒仪实验,记录小鼠步距和转棒仪停留时间。行为学测试后处死小鼠,取脑组织,采用免疫组化法行黑质多巴胺能神经元计数;采用Western blot法检测黑质α-突触核蛋白(α-Syn)和酪氨酸单氧化酶(TH)的表达。结果:与C组比较,PD组步距减小,转棒仪停留时间缩短,黑质多巴胺能神经元计数减少,黑质TH表达下调,α-Syn表达上调(P<0.05),Pro组上述各指标差异无统计学意义(P>0.05)。与PD组比较,Pro组步距增大,转棒仪停留时间延长,黑质多巴胺能神经元计数增多,黑质TH表达上调,α-Syn表达下调(P<0.05)。结论:丙泊酚对PD小鼠多巴胺能神经元具有保护作用,其机制可能与黑质α-Syn表达下调有关。
Objective To evaluate the effect of propofol on dopaminergic neurons of mice with Parkinson′s disease(PD).Methods Forty-eight pathogen-free healthy male C57BL/6 mice,aged 8-12 weeks,weighing 22-32 g,were divided into 3 groups(n=16 each)using a random number table method:control group(group C),group PD and propofol group(group Pro).The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine(MPTP)was intraperitoneally injected for 7 consecutive days in PD and Pro groups,while the equal volume of normal saline was given for 7 consecutive days in group C.At 30 min after intraperitoneal injection of MPTP,propofol 25 mg/kg was intraperitoneally injected in group Pro,while the equal volume of normal saline was given daily in group C and group PD.At day 8 after the end of establishment of the model,gait analysis system experiment and rotarod test were used to record the step distance and retention time.The animals were sacrificed after the behavioral tests,and the brain tissues were removed for the dopamine neuron count in substantia nigra(by immunohistochemistry)and for determination of the expression of alpha-Synuclein(α-Syn)and Tyrosine hydroxylase(TH)in the substantia nigra(by Western blot).Results Compared with group C,the step distance was significantly decreased,retention time were shortened,the dopamine neuron count in substantia nigra was decreased,the expression of TH was down-regulated,and expression ofα-Syn in substantia nigra was up-regulated in group PD(P<0.05),and no significant change was found in the parameters mentioned above in group Pro(P>0.05).Compared with group PD,the step distance was significantly increased,retention time were prolonged,the dopamine neuron count in substantia nigra was increased,the expression of TH was up-regulated,and expression ofα-Syn in substantia nigra was down-regulated in group Pro(P<0.05).Conclusion Propofol has protective effect on dopaminergic neurons of PD mice,and the mechanism may be related to the down-regulation ofα-Syn expression in substantia nigra.
作者
宋俊杰
王丹丹
李会芳
郑孝振
陈勇
王莹
魏建设
Song Junjie;Wang Dandan;Li Huifang;Zheng Xiaozhen;Chen Yong;Wang Ying;Wei Jianshe(Department of Anesthesiology,The First Affiliated Hospital of Henan University,Kaifeng 475000,China;Henan Medical School,Kaifeng 475000,China;School of Life Sciences,Henan University,Kaifeng 475000,China)
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2021年第6期707-710,共4页
Chinese Journal of Anesthesiology
基金
国家自然科学基金(81600940)
河南省高等学校重点科研项目(19A320021)。
