摘要
目的研究急性和亚急性1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）帕金森病小鼠模型腹侧中脑与纹状体中脂多糖受体CD14 mRNA、TLR4 mRNA的表达。方法腹腔注射MPTP制作急性（20 mg/kg,4次,每次间隔2 h）和亚急性（20 mg/kg,每天1次,共7 d）帕金森病小鼠模型。实验分为4组：正常对照组（8~10周龄小鼠）、中年小鼠组（8月龄）、急性模型组（8~10周龄）、亚急性模型组（8~10周龄）,每组6只C57BL/6小鼠。模型组小鼠在末次注射MPTP 1d后取脑组织。用酪氨酸羟化酶（TH）免疫组织化学染色,观察亚急性小鼠模型黑质多巴胺能神经元数目改变情况。用RT-PCR方法检测CD14 mRNA、TLR4 mRNA的表达水平。结果亚急性小鼠模型黑质TH阳性细胞减少。急性和亚急性模型组小鼠黑质与纹状体CD14 mRNA表达水平明显增高,高于正常对照组和中年小鼠组（均P〈0.05）,TLR4mRNA表达各组间没有明显差异（P〉0.05）。结论 CD14 mRNA作为内毒素受体在MPTP帕金森病小鼠表达增高,可能涉及脂多糖介导的免疫反应,从而参与神经损伤和帕金森病病理生理过程,针对CD14的阻断中和处理可能作为一种新的帕金森病治疗措施。
Objective To investigate the expression of CD14 and TLR4 mRNA in ventral midbrain and caudate putamen of acute and subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP）Parkinson＇s disease mouse model.Methods C57BL/6 mice were divided into 8-10-week-old group,middle-aged（8-month-old）group,acute and subacute MPTP Parkinson＇s disease model group（8-10-week-old）.Model mice were intraperitoneally injected with MPTP（20 mg/kg）once daily for consecutive 7 days or received 4 intraperitoneal injections of MPTP（20 mg/kg）at 2-h intervals and were sacrificed one day after the last injection.Control mice（8-10-week-old group and middle-aged group）received saline solution only.Dopaminergic neuron loss of subacute mice model was observed by using TH staining.The expression of CD14 mRNA and TLR4 mRNA in these samples were analyzed by RT-PCR.Results The number of TH positive cells was decreased after MPTP treatment.The expression of CD14 mRNA but not TLR4 mRNA was increased in the ventral midbrain and caudate putamen of mice treated with MPTP（both acute and subacute Parkinson＇s disease models）in comparison to untreated animals.Conclusion The overexpression of CD14 mRNA suggests that the endotoxin receptors may be non-specific neuroinflammatory phase,and possible involvement of inflammatory response in the pathophysiology of Parkinson＇s disease.
出处
《华中科技大学学报（医学版）》
CAS
CSCD
北大核心
2010年第6期775-779,共5页
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
