摘要
目的 研究生酮饮食对PD小鼠黑质多巴胺能神经元的抗凋亡作用。方法1-甲基-4-苯基-1、2、3、6-四氢吡啶（MPTP）腹腔注射方法制备PD模型小鼠。实验分为正常饮食模型组（正常饮食喂养后造模）、实验组（生酮饮食喂养后造模）、正常饮食组（不造模，正常饮食喂养）和生酮饮食组（不造模，生酮饮食喂养1。初次MPTP给药前及末次给药后的次日进行滚轴实验并采集血清样本检测血清酮体和血糖浓度。荧光定量PCR技术检测黑质酪氨酸羟化酶（TH）、Bcl-2及caspase-3基因水平的表达情况。结果经过生酮饮食喂养后的小鼠经MPTP给药后，死亡率较正常饮食模型组降低：滚轴实验中实验组在转盘上停留时间较正常饮食模型组延长，差异均有统计学意义（P〈0．05）。实验组和生酮饮食组的血清酮体浓度较其他2组明显升高，差异有统计学意义（P〈0．05）。荧光定量PCR检测发现，与正常饮食模型组相比，实验组黑质中册基因的表达明显升高，抗凋亡作用的Bcl-2基因也明显升高，促凋亡作用的caspase-3基因的表达明显减少，差异均有统计学意义（P〈0．05）。结论生酮饮食逆转了MPTP给药后的黑质中Bcl-2基因表达的下调和caspase-3基因表达的上调．进而抑制了多巴胺能神经元的凋亡，起到了保护黑质多巴胺能神经元的作用。
Objective To investigate the anti-apoptotic effect of ketogenic diet （KD） on substantia nigra dopaminergic neurons in mouse models with PD. Methods Eight-week-old male C57BL/6 mice, weighting 24-26 g, were randomly divided into normal diet and model group （1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine [MPTP]）, experimental group （KD＋MPTP）, normal diet group and KD group. Mouse models with PD were established by subjecting them to intraperitoneal injection of MPTP. All the mice in the normal diet group and MPTP group were fed with normal diet and were flee to access food, while mice in the KD＋MPTP and KD group were fed with KD every other day for 1 month. All mice were trained for rotarod test during the feeding and time on the rotarod was formally recorded 1 d before the drug injection. One d after the last injection, rotarod test was implemented again, and then, samples of blood were collected for analysis of serum concentrations of ketone bodies and glucose. The levels of substantia nigra TH, Bcl-2 and caspase-3 gene expressions were examined by fluorescence quantitative PCR. Results The mice in the KD＋MPTP group not only enjoyed a lower mortality rate, but also performed better in the rotarod test than mice in the MPTP group. The concentrations of serum ketone bodies in the KD group and KD＋MPTP group were significantly higher than those in the other 2 groups （P〈0.05）. Compared with the MPTP group, the levels of TH and Bc1-2 gene expressions in the KD＋MPTP group were significantly increased, while the level of caspase-3 gene expression was significantly reduced （P〈0.05）. Conclusion KD reverses the effect of MPTP administration by decreasing the level of Bc1-2 gene expression and increasing the level of caspase-3 gene expression, therefore, it inhibits the apoptosis of dopaminergic neurons and plays a vital role in the protection of substantia nigra dopaminergic neurons.
出处
《中华神经医学杂志》
CAS
CSCD
北大核心
2010年第10期1018-1022,共5页
Chinese Journal of Neuromedicine
关键词
帕金森病
生酮饮食
酪氨酸羟化酶
BCL-2
CASPASE-3
Parkinson＇s disease
Ketogenic diet
1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine
Bcl-2 gene
Caspase-3 gene
