丙泊酚对帕金森小鼠黑质多巴胺能神经元凋亡的影响  

The effect of propofol on apoptosis of dopaminergic neurons in the substantia nigra of mouse model of Parkinson's disease

作　　者：余志阳[1] 潘士勇[2] 刘清珍[1] 刘健[1] 陈春龙[1] 李伟彦[1] 朱四海[1] 

机构地区：[1]南京军区南京总医院麻醉科,江苏南京210002 [2]南京军区南京总医院干部保健科,江苏南京210002

出　　处：《东南国防医药》2015年第4期346-348,371,共4页Military Medical Journal of Southeast China

基　　金：南京军区面上课题(12MA091);南京军区南京总医院面上课题(2013026)

摘　　要：目的观察丙泊酚对帕金森病(Parkinsons disease,PD)模型小鼠黑质多巴胺能神经元凋亡及半胱氨酸蛋白酶-3(caspase-3)、Bcl-2蛋白表达的影响。方法雄性C57BL6小鼠48只,随机分为等渗盐水对照组、PD模型组、PD模型+2 h脂肪乳组、PD模型+24 h脂肪乳组、PD模型+2 h丙泊酚组、PD模型+24 h丙泊酚组。腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)30 mg/kg,连续5 d,建立小鼠PD模型。最后一次注射MPTP后分别于2 h、24 h腹腔注射脂肪乳(10 m L/kg)或丙泊酚(100 mg/kg)。最后一次腹腔注射药物后12 h后处死小鼠取中脑黑质区。采用免疫组化方法观察黑质区神经元凋亡情况,采用免疫蛋白印迹法检测Caspase-3、Bcl-2蛋白的表达水平。结果与对照组比较,PD组模型及脂肪乳组,小鼠的黑质神经元凋亡细胞均明显增加,同时凋亡相关蛋白Caspase-3表达明显升高,而抗凋亡蛋白Bcl-2的水平明显下降。与脂肪乳组相比,丙泊酚组小鼠的黑质神经元凋亡细胞均明显减少,同时凋亡相关蛋白Caspase-3表达水平明显减低,而抗凋亡蛋白Bcl-2的水平明显上升,且分子表达改变在模型建立24 h后给予丙泊酚更显著。结论丙泊酚能减少PD小鼠黑质多巴胺能神经元凋亡,同时上调抗凋亡蛋白Bcl-2表达,下调促凋亡蛋白Caspase-3蛋白的表达,丙泊酚通过调控凋亡相关蛋白表达水平产生脑保护作用。Objective To observe the effect of propofol on neuronal apoptosis and expression of Caspase-3 and Bcl-2 protein in the substantia nigra of mouse model of Parkinson＇s disease.Methods A total of forty eight male C57BL6 mice were randomly as-signed to six groups：group I control, the remaining five groups were firstly to establish mouse model of Parkinson＇s disease （ PD） with intraperitoneal injection of 1-methyl -4-phenyl-1, 2, 3, 6-tetrahydropyridine （ MPTP） 30 mg/kg for five consecutive days.Intralipos （10 mL/kg） or propofol （100 mg/kg） was respectively administered intraperitoneal injection in 2 h or 24 h after establishtion of PD. The mice were sacrificed to take the substantia nigra after the last 12 h intraperitoneal injection of drugs.Apoptosis was observed in sub-stantia nigra with immunohistochemistry, and the expression of Bcl-2 and protein ysteine proteinase-3 were tested with Western blot. Results Compared with the mice in control group, the mice in PD group and intralipos group of apoptosis neurons were significantly increased in substantia nigra of mice, while the expression of protein Caspase-3 was increased significantly and the levels of the anti-apoptotic protein Bcl-2 decreased obviously.The mice in popofol groups of apoptosis neurons were significantly decreased, compared with the mice in intralipos groups, however, expression of protein Caspase-3 apoptosis related was decreased significantly and the levels of the antiapoptotic protein Bcl-2 increased obviously, and the change of molecular expression was more significant in 24 h when the propofol was administered after establishment of PD model.Conclusion Propofol can reduce apoptosis in dopaminergic neurons PD of substantia nigra in PD mice, and upgrade expression of antiapoptotic protein Bcl-2, downgrade expression of apoptosis protein Caspase 3.Expression level of proteins apoptosis related was regulated to produce cerebral protection by propofol.

关 键 词：帕金森病 凋亡 丙泊酚 半胱氨酸蛋白酶-3 BCL-2 

分 类 号：R742.5[医药卫生—神经病学与精神病学]