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目的:观察DJ-1缺失和出生前脂多糖(lipopolysaccharide,LPS)暴露对出生后小鼠多巴胺能(dopam-inergic,DA)系统和神经炎症的影响。方法:妊娠第10.5 d DJ-1基因敲除的小鼠腹腔注射脂多糖(10,000 EU/kg体重)后自然分娩的后代在4月和14月龄时处死。免疫组织化学染色结合体视学计数定量黑质酪氨酸羟化酶(Tyrosine hydroxylase,TH)和CD11b阳性细胞数量。高效液相色谱法测定纹状体DA代谢物水平。免疫荧光法测定TNF-α和IL-1β蛋白水平。结果:4月和14月龄的DJ-1基因敲除的小鼠均没有明显的DA神经元减少和脑内神经炎症改变。出生前接触过LPS的4月和14月龄野生型小鼠,黑质DA能神经元分别减少13.6%和23.1%,纹状体DA含量分别减少19.0%和26.2%,同时神经炎症改变明显。出生前接触过LPS的4月和14月龄DJ-1基因敲除小鼠,黑质DA能神经元分别减少22.5%和35.4%,纹状体DA含量分别减少34.3%和39.3%,同时脑内炎症反应更明显。结论:以上结果提示遗传因素缺失和环境因素可能共同引发帕金森病发生,进一步验证了帕金森病多因素损伤引发的发病假说。
Objective: To observe the effects of DJ-1 deficiency and lipopolysaccharide (LPS) exposure on dopaminergic system and neuroinflammation in postnatal mice. METHODS: Progeny of spontaneous childbirth after intraperitoneal injection of lipopolysaccharide (10,000 EU / kg body weight) on day 10.5 of DJ-1 knockout mice were sacrificed at April and 14 months of age. Immunohistochemical staining combined with somatostatin count to quantify the number of Tyrosine hydroxylase (TH) and CD11b positive cells. Determination of striatum DA metabolites by high performance liquid chromatography. The levels of TNF-α and IL-1β were measured by immunofluorescence. RESULTS: There was no significant decrease in DA neurons and neuroinflammation in the DJ-1 knockout mice at April and 14 months of age. In April and 14-month-old wild-type mice exposed to LPS prior to birth, DA neurons in the substantia nigra were reduced by 13.6% and 23.1%, respectively, and DA content in the striatum decreased by 19.0% and 26.2%, respectively, with significant changes in neuroinflammation. In April and 14-month-old DJ-1 knockout mice exposed to LPS before birth, DA neurons in the substantia nigra were reduced by 22.5% and 35.4%, while striatum DA content was decreased by 34.3% and 39.3%, respectively Within the inflammatory response is more obvious. Conclusion: The above results suggest that genetic loss and environmental factors may jointly trigger the occurrence of Parkinson’s disease, which further validates the hypothesis caused by multiple factors of Parkinson’s disease.