CAJ | 학술논문

目的：观察丙泊酚对帕金森病（ Parkinson蚕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 mL／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。
목적：관찰병박분대파금삼병（ Parkinson잠s disease，PD）모형소서흑질다파알능신경원조망급반광안산단백매-3（ caspase-3）、Bcl-2단백표체적영향。방법웅성C57BL6소서48지，수궤분위등삼염수대조조、PD모형조、PD모형＋2 h지방유조、PD모형＋24 h지방유조、PD모형＋2 h병박분조、PD모형＋24 h병박분조。복강주사1-갑기-4-분기-1，2，3，6-사경필정（MPTP）30 mg／kg，련속5 d，건립소서PD모형。최후일차주사MPTP후분별우2 h、24 h복강주사지방유（10 mL／kg）혹병박분（100 mg／kg）。최후일차복강주사약물후12 h후처사소서취중뇌흑질구。채용면역조화방법관찰흑질구신경원조망정황，채용면역단백인적법검측Caspase-3、Bcl-2단백적표체수평。결과여대조조비교，PD조모형급지방유조，소서적흑질신경원조망세포균명현증가，동시조망상관단백Caspase-3표체명현승고，이항조망단백Bcl-2적수평명현하강。여지방유조상비，병박분조소서적흑질신경원조망세포균명현감소，동시조망상관단백Caspase-3표체수평명현감저，이항조망단백Bcl-2적수평명현상승，차분자표체개변재모형건립24 h후급여병박분경현저。결론병박분능감소PD소서흑질다파알능신경원조망，동시상조항조망단백Bcl-2표체，하조촉조망단백Caspase-3단백적표체，병박분통과조공조망상관단백표체수평산생뇌보호작용。
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.