实用医学杂志 ›› 2021, Vol. 37 ›› Issue (9): 1106-1116.doi: 10.3969/j.issn.1006⁃5725.2021.09.002

• 基础研究 • 上一篇    下一篇

异常增加的α⁃突触核蛋白对帕金森病模型小鼠黑质及结肠多巴胺受体D1的表达影响

徐晓峰, 罗汉将, 莫琼, 左丽丝, 黄秀仙, 陈敏    

  1. 桂林医学院附属医院神经科学实验室,广西神经系统疾病临床研究中心,广西脑与认知神经科学重点实 验室(广西桂林 541001)

  • 出版日期:2021-05-10 发布日期:2021-05-10
  • 通讯作者: 陈敏 E⁃mail:chenmin790830@163.com
  • 基金资助:

    国家自然科学基金资助项目(编号:81760241);广 西科技计划项目(编号:桂科AB18221039,2017GXNSFBA198019); 广西高校中青年教师基础能力提升项目(编号:2018KY0409);广 西医疗卫生事宜技术开发与推广应用项目(编号:S2017112);大 学生创新创业训练计划项目(编号:201810601056,201810601059 

Effect of abnormally increased α⁃ synuclein on the expression of dopamine receptor D1 in the substantia nigra and colon of Parkinson′ s disease model mice

XU Xiaofeng,LUO Hanjiang,MO Qiong,ZUO Lisi HUANG Xiuxian,CHEN Min   

  1. Neuroscience Laboratory,Affiliated Hospital of Guilin Medical University Hospital Guangxi Key Laboratory of Brain and Cognitive Neuroscience,Guangxi Clinical Research Center for Neurological Dis⁃ eases,Guilin 541001,China

  • Online:2021-05-10 Published:2021-05-10
  • Contact: CHEN Min E⁃mail:chenmin790830@163.com

摘要:

目的 探讨异常增加的α⁃突触核蛋白(α⁃Syn)对小鼠脑及结肠多巴胺受体 D1(D1DR)表达的影响。方法  C57BL/6J 小鼠随机分为对照及模型组,纹状体立体定位注射α⁃Syn 预成型纤维(PFF)制备小鼠帕金森病(PD)模型,对照组注射等体积 PBS;术后 6 个月进行平衡杆、爬杆及旷场实验检测小鼠行为学差异;通过 Western blot(WB)、免疫组化及免疫荧光检测黑质及结肠 D1DR、α⁃Syn、酪氨酸羟化酶 TH)的表达情况。结果 与对照组相比,模型组小鼠出现平衡杆和爬杆运动时间延长、旷场平均运动速 度减慢(P < 0.001)等运动迟缓表现;WB、免疫组化及免疫荧光结果显示,模型组小鼠黑质及结肠 D1DR TH 阳性细胞明显减少(均 P < 0.05),表达较对照组均下降(均 P < 0.05),且在黑质与结肠中的相对表达量呈正相关(r = 0.8943、0.9026,P < 0.05)。结论 通过脑纹状体注射α⁃Syn PFF 建立的 PD 模型小鼠黑质及 结肠中D1DR、TH 表达降低,为结肠活检应用于评估早期PD 患者中枢神经病理提供了实验基础。

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Abstract:

Objective To investigate the effect of abnormally increased α ⁃synuclein(α ⁃Syn)on the expression of Dopamine receptor D1(D1DR)in the brain and colon of mice. Methods Sixteen C57BL/6J mice were randomly divided into control and model groups:the model group was injected with α⁃Syn preformed fibrils (PFF)into the striatum to build a mouse Parkinson′s disease(PD)model,and the control group with equal volume of PBS. Balance beam,pole ⁃ climbing and open field tests were performed to detect their behaviors at 6 months after operation;Western blot(WB),immunohistochemistry(IHC)and immunofluorescence(IF)were used to detect the expressions of D1DR,α⁃Syn,and tyrosine hydroxylation(TH)in the substantia nigra and colon. Results Compared with the controls,the model mice exhibited prolonged time in balance beam and pole⁃climbing (P < 0.001),and slower average moving speed in open field test(P < 0.001). By WB,IHC and IF,the D1DR and TH positive cells were significantly reduced in number(all P < 0.05)and the expressions of D1DR and TH in the substantia nigra and colon of the model mice were lower than those in the control group(all P < 0.05). The relative expression in the substantia nigra and colon was positively correlated(r = 0.8943,0.9026,P < 0.05). Conclusion The expressions of D1DR and TH are decreased in the substantia nigra and colon of PD model mice built by injection of α⁃Syn PFF into the striatum,which provides a basis for application of colon biopsy to the path⁃ological assessment of central nerves of early PD patients. 

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