褪黑素对帕金森病模型大鼠代谢机能和DA能神经元的保护作用

The protective effect of melatonin on dopaminergic neurons and on the metabolic function in rats with Parkinson disease

目的我们前期研究证实6-羟基多巴胺(6-OHDA)明显诱导性帕金森病(PD)模型大鼠行为学障碍及其纹状体神经元的损伤。目前进一步借助褪黑素(MT)探查证实6-羟基多巴胺对PD模型大鼠纹状体代谢机能损害和黑质DA能神经元的保护作用。方法选取55只成年雄性SD大鼠,并随机分成正常对照组(包括正常对照和稀释剂对照)、6-OHDA处理组和6-OHDA+MT处理组,实验借助Micro PET-CT、免疫组织化学染色及Westernblot技术检测和比较实验大鼠纹状体代谢、TH阳性纤维密度及TH蛋白表达量的变化。所获得数据使用SPSS20.0统计学软件进行分析处理,P<0.05为有统计学意义。结果 Micro PET-CT检测结果显示,6-OHDA组大鼠纹状体糖代谢机能(1.34±0.114)明显较对照组(4.36±0.114)低(P=0.00),而6-OHDA+MT处理组(4.14±0.114)与6-OHDA组相比糖代谢机能增高,差异也具有统计学意义(P=0.00)。纹状体内TH阳性纤维密度和TH蛋白表达水平在6-OHDA组(分别为0.324±0.018、0.434±0.338)均显著低于对照组(0.378±0.026、1.626±0.526)(P=0.00,P=0.00)和6-OHDA+MT处理组(0.37±0.010、1.136±0.494)(P=0.00,P=0.03),但对照组和6-OHDA+MT处理组之间差异无统计学意义(P=0.52,P=0.12)。结论褪黑素对PD模型大鼠纹状体代谢机能障碍和中脑黑质DA能神经元损伤具有一定的保护作用。

Objective Our previous studies showed that 6-hydroxydopamine （6-OHDA） evidently induced behavioral disor- ders and damage of striatal neurons in rats with Parkinson＇ s disease. Further study was conducted to explore the effects of melatonin on dopaminergic nerve cells and on the metabolic function in rats with Parkinson＇ s disease induced by 6-hydroxydopamine. Meth- ods 55 male adult SD rats were randomly divided into three groups ： control group, 6-OHDA group and 6-OHDA＋MT group. Micro PET-CT, immunohistochemistry technique and Western-blot was used to detect the changes ofglycometabolism, density of TH immunoreactive fibers and TH protein expression. The data were analyzed with SPSS. Results Micro PET-CT revealed that, compared to control group（4.36±0.114） and 6-OHDA＋MT group（4.14±0.114）, 6-OHDA group（ 1.34±0.114）significantly had glycometabolism hypofunction （P=0.00, P=0.00）, control group and 6-OHDA ＋ MT group showed no significantly difference （P=0.10）. In addition, there is a significant reduction in TH immunoreactive fibers and TH protein expression for 6-OHDA group （0.324±0.018, 0.434±0.338 respectively）, compared with control group 0.378±0.026, 1.626±0.526）（P=0.00, P=0.00）and 6-OHDA＋MT （0.37±0.010, 1.136±0.494）（P=0.00, P=0.03） , control group and 6-OHDA ＋ MT group showed no significantly difference （P--0.52,P= 0.12） .Conclusion Melatonin could protect metabolic function of rats and prevent the damage of dopaminergic nerve fibers.