甲氰菊酯联合多巴胺对小鼠多巴胺能神经通路的影响

The toxic effect of fenpropathrin and dopamine on dopaminergic system of mice

目的观察甲氰菊酯(Fenpropathrin,Fen)单独腹腔注射及与多巴胺(Dopamine,DA)立体定向注射联合使用对C57BL小鼠黑质纹状体多巴胺能神经通路的影响。方法分别采用Fen腹腔注射、DA立体定向注射至纹状体及DA预处理联合Fen注射建立C57BL小鼠模型,观察小鼠行为学变化,HPLC检测脑组织内Fen的含量;激光共聚焦显微镜观察小鼠的黑质多巴胺能神经元及纹状体的TH染色。结果 Fen及DA分别单独使用及DA预处理联合Fen注射均造成小鼠自主活动能力减少,HPLC检测显示小鼠脑组织中Fen的浓度与腹腔Fen给药浓度成正比,TH染色发现Fen连续使用7 d和DA立体定向注射后第7 d的小鼠黑质均出现神经元中TH表达不均一,并且纹状体出现斑片状的TH染色丢失,其中DA预处理后使用Fen注射7d组改变最明显。结论 Fen能够透过小鼠血脑屏障,可以直接作用于小鼠黑质纹状体多巴胺能系统,并且可以明显增强DA对黑质纹状体的损伤作用。

Objective To explore and compare the effects of fenpropathrin intraperitoneal injection or combined with DA stereotacical injection on dopamine system of mice. Methods Fenpropathrin was injected intraperitoneally or combined with the DA stereotactically injected at the striatum of the mouse brain. The behaviors features of animals were investigated using pole jumping test and head up test. HLPC was used to detect the fenpropathrin in the mice brain after fenpropathrin intraperitoneal injection. The immunoreactivity of tyrosine hydroxylase in the brains were observed by immunohistochemistry. Results Behavior investigation indicated that both fenpropathrin intraperitoneal injection or combined with the DA stereotactically injection could decrease the mice＇s activity. Fenpropathrin was dectected in the brain by HPLC. Immunohistochemistry study suggested that the tyrosine hydroxylase immunoreactivity were decreased in striatum of fenpropathrin combined with the DA group. DAT immunoreactivity were increased in the striatum after fenpropathrin exposure. Conclusion Fenpropathrin could cross the blood brain barrier,enhanced the toxicity of DA on dopamine system.