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目的采用腹腔注射LPS的方法建立慢性帕金森病小鼠模型,评价该模型小鼠行为学特点、黒质多巴胺能神经元损毁情况及小胶质细胞活化数量的改变。方法将48只雄性C57BL/6小鼠随机分为2组,模型组给予单次腹腔注射LPS(5 mg/kg),对照组以相同方法注射生理盐水(5 mg/kg)。分别于处理后的第1个月末、第3个月末、第5个月末和第7个月末每组随机选出6只小鼠,采用转棒实验及旷场试验观察小鼠行为学变化情况,免疫组织化学染色法观察小鼠黒质区酪氨酸羟化酶(TH)阳性细胞及IBA-1阳性细胞(活化的小胶质细胞)数目的变化。结果与对照组相比,从第3个月末开始至第7个月末LPS组小鼠均出现明显的PD行为表现,运动能力明显下降(P<0.05),中脑黒质区多巴胺能神经元数量减少显著(P<0.01);IBA-1阳性细胞数则在1月末就出现明显升高(P<0.01),且一直持续到实验结束。结论腹腔注射LPS能够引起持续性的小胶质细胞活化,并可诱导较为稳定的慢性帕金森病小鼠模型。
Objective To establish a mouse model of chronic Parkinson’s disease by intraperitoneal injection of LPS and evaluate the behavioral characteristics, the damage of dopaminergic neurons and the activation of microglia in this mouse model. Methods 48 male C57BL / 6 mice were randomly divided into 2 groups. The model group received single intraperitoneal injection of LPS (5 mg / kg), and the control group received normal saline (5 mg / kg) by the same method. At the end of the first month, the end of the third month, the end of the fifth month and the end of the seventh month, 6 mice were randomly selected in each group. The behavioral changes of the mice were observed under the condition of rotating bar test and open-field test. Immunohistochemical staining was used to observe the changes of tyrosine hydroxylase (TH) positive cells and IBA-1 positive cells (activated microglia) in the substantia nigra of mice. Results Compared with the control group, the mice in LPS group showed significant PD behavior at the end of the third month and the end of the seventh month, the exercise capacity decreased significantly (P <0.05), the number of dopaminergic neurons (P <0.01). The number of IBA-1 positive cells increased significantly at the end of January (P <0.01), and continued until the end of the experiment. Conclusion Intraperitoneal injection of LPS can induce persistent microglial activation and induce a more stable mouse model of chronic Parkinson’s disease.