关键词: 脂多糖, 黑质, 炎性因子, 神经递质, 免疫组织化学, 免疫印迹法, 高压液相色谱法, 恒河猴

Abstract: Objective To observe the neurodegenerative effects of inflammation, induced by intra-cerebral injection of lipopolysaccharide (LPS) on dopaminergic neurons in the substantia nigra of rhesus mI>onkey/I>, in order to explore the relations of mechanism of Parkinsonism with activation of microglia and the releasing of inflammatory factors in the animal brain. Methods Eight adult rhesus mI>onkey/I>s were divided into an acute experimental group and a chronic experimental group. Among them 3 mI>onkey/I>s were used for acute experiment. They were unilaterally injected with LPS and survived for 1 week to demonstrate the changes of tyrosine hydroxylase(TH) expression and inflammatory factor release by Western blotting analysis. The other 5 mI>onkey/I>s were used for chronic experiment and 4 of them were intranigrally injected with LPS and survived for 24 weeks and 48 weeks respectively after the injection. Only one mI>onkey/I> was injected with saline as a control animal. The injections were stereotaxically made 3 times(at weeks 0，8，16 respectively) in the substantia nigra on one side. The number of TH-positive neurons was detected by TH immunohistochemistry and the nigro-striatal levels of neurotransmitters were determined by high pressure liquid chromatogram (HPLC). Result In the acute experimental group of mokeys: no obvious changes of TH expressing could be seen either on the injection side and control side, but it was shown the activation of microglia and increasing expression of HLA-DR TNF-α，IL-1β and COX-2 in the substantia nigra on injected side. In the chronic experimental group of mokeys， however, the number of TH-positive neurons in the injected substantia nigra and neurotransmitters levels in the nigro-striatal area were decreased. No obvious changes could be seen in the control case of saline injected mI>onkey/I>. Conclusion LPS injection in the substantia nigra of the primate causes severe inflammation in one week, which may lead to a

Key words: Lipopolysaccharide, Substantia nigra, Inflammatory factor, Neurotransmitter, Immunohistochemistry, Western blotting, HPLC, Rhesus