脂多糖诱导的慢性帕金森病小鼠模型α-突触核蛋白的出现和转移变化

目的: 建立脂多糖（LPS）诱导的慢性帕金森病(PD)小鼠模型，探讨PD模型小鼠的行为学改变和肠壁中α-突触核蛋白聚集物的出现和转移变化情况。方法: 将48只雄性C57BL/6J小鼠，6周龄，随机分为生理盐水对照组、PD 模型组。采用腹腔注射LPS制备PD小鼠模型，通过转棒实验和旷场试验检测小鼠的行为学变化；通过免疫组化技术，观察PD模型组小鼠多巴胺能神经元丢失和α-突触核蛋白出现和转移变化。结果: PD模型小鼠行为学改变与生理盐水对照组具有差异性（P<0.01）；PD模型组小鼠的中脑黑质致密部的多巴胺能神经元出现严重损失；α-突触核蛋白（α-Syn）聚集最先出现在肠道，随着时间的延长，α-Syn转移到中脑黑质致密部。结论: 在LPS诱导的PD模型中，其典型的病理改变（α-Syn的沉聚）起始于结肠神经，并逐渐发展到中脑黑质致密部,进而导致多巴胺能神经元的损伤与丢失。

LPS-induced chronic Parkinson's disease in mice α-synuclein in the emergence and metastasis

AIM: To establish a mouse model of chronic Parkinson's disease(PD) induced by lipopolysaccharide (LPS) and to investigate the behavioral changes of PD mice and the appearance and metastasis of α-synuclein(α-Syn) aggregates in the intestinal wall. METHODS: 48 male C57BL/6J mice were randomly divided into normal saline control group and PD model group at 6 weeks of age. The PD mice model was established by intraperitoneal injection of LPS. Behavioral changes of the experimental mice were detected by the rotating bar test and field test. The dopaminergic neuron loss and α-Syn were observed by immunohistochemistry nuclear protein expression and metastasis. RESULTS:Behavioral changes of PD model mice exhibited significance difference (P<0.01). PD model mice's substantia nigra pars compacta α-Syn aggregation first appeared in the gut, and over time, the α-Syn was transferred to the substantia nigra of the mesencephalon, and the dopaminergic neurons were severely damaged. CONCLUSION: In the LPS-induced PD model, the typical pathological changes (α-Syn aggregation) begin in the colon nerves, and gradually develop into the substantia nigra pars compacta, resulting in dopaminergic neuron damage and loss.