维生素D_(3)对帕金森病小鼠的保护作用及机制研究

Study on the protective effect and mechanism of VD_(3) in mice with Parkinson’s disease

目的探讨维生素D_(3)(VD_(3))对帕金森病小鼠黑质-纹状体系统的保护作用及机制。方法C57BL/6J雄性小鼠随机分为5组:对照组、模型组、VD_(3)低剂量组、VD_(3)中剂量组和VD_(3)高剂量组。通过连续腹腔注射7 d 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)20 mg/kg,制备PD小鼠。VD_(3)低、中、高剂量组分别腹腔注射VD_(3)(0.5、1.0、2.0μg/kg)21 d。通过爬杆试验、滚轴试验检测小鼠的行为学;qPCR检测黑质α-突触核蛋白(α-syn)、酪氨酸羟化酶(TH)的mRNA表达水平。Western Blot检测黑质α-syn、TH的表达水平。结果与对照组比较,模型组小鼠停留时间、爬杆时间延长,转轴时间缩短;黑质α-syn升高、TH下降,差异均有统计学意义(P<0.05);与模型组比较,中、高剂量组小鼠的停留时间、爬杆时间缩短,转杆时间延长;黑质α-syn的m RNA及蛋白表达水平下降、TH的m RNA及蛋白表达水平升高,差异均有统计学意义(P<0.05)。结论VD_(3)通过抑制黑质α-syn、升高TH活性,发挥对帕金森病小鼠的保护作用。

Objective To investigate the protective effect and mechanism of vitamin D_(3)(VD_(3))on the substantia nigrastriatum system in mice with Parkinson’s disease(PD).Methods C57BL/6J male mice were randomly divided into five groups,namely,the control group,the model group,the low-dose VD_(3)group,the medium-dose VD_(3)group and the high-dose VD_(3)group.Those mice were injected intraperitoneally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)(20 mg/kg)for 7 consecutive days to establish PD models of mice.The low-dose VD_(3)group,the medium-dose VD_(3)group and the high-dose VD_(3)group were injected intraperitoneally with VD_(3)of 0.5μg/kg,1.0μg/kg,and 2.0μg/kg respectively for 21 consecutive days.The behavior of mice was examined by pole-climbing test and roller test.The mRNA expression levels ofα-synuclein(α-syn)and tyrosine hydroxylase(TH)in substantia nigra were detected by quantitative polymerase chain reaction(qPCR).In addition,the expression levels ofα-syn and TH in substantia nigra were detected by Western Blot.Results Compared with the control group,the residence time and pole-climbing time of mice were prolonged and the rotation time was shortened in the model group,while the level ofα-syn was elevated and TH was decreased,with statistically significant differences(P<0.05).Compared with the model group,the residence time and pole-climbing time of mice were shortened and the rotation time was prolonged in the mediumdose VD_(3)group and the high-dose VD_(3)group.Meanwhile,compared with the model group,the mRNA and protein expression levels ofα-syn in substantia nigra were decreased,while those of TH were increased in the medium-dose VD_(3)group and the high-dose VD_(3)group,all with statistically significant differences(P<0.05).Conclusion VD_(3)exerts a protective effect on mice with PD by inhibitingα-syn and increasing TH activity.