【摘要】 目的:研究CD4+T细胞上的多巴胺D2受体(dopamine receptor D2, DRD2)对帕金森病(Parkinson′s disease,PD)模型小鼠的影响。方法:条件性敲除CD4+T细胞DRD2基因的雄性小鼠(CD4-Cre Drd2fl/fl)、C57BL/6小鼠通过腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methy-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP)制备PD模型,注射7 d后,用旷场实验法来测量小鼠运动的平均速度,再无菌取小鼠脾脏,制备单个核细胞悬液,用Trizol法提取细胞总RNA,然后用实时荧光定量聚合酶链式反应法检测小鼠脾脏单个核细胞中的促炎因子白细胞介素(interleukin, IL)-17、干扰素γ(interferonγ, IFN-γ)和抗炎因子IL-4、转化生长因子-β1(transforming growth factor-β1, TGF-β1)的表达。用流式细胞术来检测脾脏中CD4+T细胞占单个核细胞的百分比。结果:CD4-Cre Drd2fl/fl PD模型小鼠旷场运动速度较野生型PD模型小鼠减慢,脾脏中CD4+T细胞占单个核细胞的百分比较野生型PD模型小鼠降低,脾脏单个核细胞中IL-17、IFN-γ的mRNA表达均高于野生PD模型小鼠,IL-4、TGF-β1的mRNA表达没有明显变化。结论:条件性敲除CD4+T细胞DRD2基因加重了PD模型小鼠的病变及外周炎症的变化。更多还原

【Abstract】 Objective: To explore the effects of dopamine receptor D2(DRD2) expressed on CD4~+T cells on mouse model of Parkinson′s disease(PD). Methods: Male C57BL/6 mice and conditional knockout DRD2 gene in CD4~+T mice(CD4-Cre Drd2fl/fl)were intraperitoneal injection of 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) to prepare PD model. After 7 days, use open-field test to measure the average speed of walking in mice, and take the mice spleen preparation of mononuclear cell suspension, Trizol method of total RNA extracted cells, and then use the real-time fluorescence quantitative polymerase chain reaction method to detect the expression of mice spleen mononuclear cells pro-inflammatory factor interleukin(IL)-17, interferon γ(IFN-γ) and anti-inflammatory factor IL-4, transforming growth factor-β1(TGF-β1). Flow cytometry to detect the percentage of CD4~+T cells in spleen mononuclear cells. Results: CD4-Cre Drd2fl/flPD model mice move slowier than wild type PD model mice, the percentage of CD4~+T cells in splenic mononuclear cells comparative lower than wild type PD model mice, the expression of IFN-γ and IL-17 in splenic mononuclear cells is higher than wild PD model mice. But TGF-β1 and IL-4 have no obvious change. Conclusion: Conditional knockout DRD2 gene in CD4~+T cell aggravates the lesion and peripheral inflammation in PD.更多还原