摘要
目的 研究胰高血糖素样肽-1类似物（Val8） GLP-1-Glu-PAL对MPTP诱导的帕金森病小鼠模型黑质区多巴胺能神经元的保护作用.方法 取10～12周健康雄性C57/BL6小鼠56只,采用随机数字表法随机分为对照组（Control组）,模型组（MPTP组）,单纯注药组（Val8组）与治疗组（MPTP＋Val8组）.MPTP组腹腔注射MPTP （30 mg/kg＆#183;d）,同时Control组给予等体积0.9％生理盐水,Val8组腹腔注射（Val8） GLP-1-Glu-PAL（25 nmol/kg）,MPTP＋Val8组注射完MPTP后1h后注射（Val8） GLP-1-Glu-PAL,连续8d.每天药物注射完2h后进行游泳实验及转棒实验以观测小鼠行为变化.第8天行为学测试完1h后处死小鼠,免疫组化法检测小鼠黑质致密部酪氨酸羟化酶（Tyrosine hydroxylase,TH）阳性细胞数.结果 MPTP成功诱导了帕金森病模型,第1天到第8天,MPTP组与Control组相比,小鼠的游泳评分[（1.715±0.143）分]及掉落潜伏期[（68.048±7.823）分]明显降低,差异有统计学意义（P＜0.05）,而黑质致密部TH阳性细胞也明显减少（P＜0.01）;MPTP＋Val8组小鼠的游泳评分[（1.120±0.143）分]及掉落潜伏期[（20.546±7.823）分]则优于MPTP组,差异有统计学意义（P＜0.05）,并且TH阳性细胞数显著增多（P＜0.01）.结论 （Val8） GLP-1-Glu-PAL对MPTP所致的帕金森病小鼠黑质区多巴胺能神经元具有保护作用.
Objective To investigate the protective effects of （Val8）GLP-1-Glu-PAL to dopaminergic neurons on PD mice induced by MPTP.Methods 56 male C57BL/6 mice which are 10-12 weeks old were randomly divided into Control,model （MPTP）,muti-injection （Val8） and therapy （MPTP ＋ Val8） groups by random number table method.Mice in MPTP group were received MPTP IP.treatment （30mg/kg ＆#183; d）,the control group were treated with 0.9% saline with the same volume,Val8 group were injected with （Val8） GLP-1-Glu-PAL （25 nmol/kg）,and MPTP＋Val8 group were going to received （Val8）GLP-1-Glu-PAL 1 h after treatment of MPTP,all the groups were treated for 8 consecutive days.Behavior test were processed 2h after drug IP injection,including swimming test and rotarod test.Mice were sacrificed immediately 1h after the final trail of behavior test in 8th day,brains were withdraw for IHC assay which tested the number TH positive neurons in SNpc area.Results The classical PD behavior symptom were induced by MPTP,from 1 st to 8th,the swimming score（1.715±0.143 and dropping latency（68.048±7.823） were both decreasing compared with control.The differences were statistically significant （P〈0.05）.The positive dopaminergic neurons were significantly lower in SNpc area （P〈0.01）.Compared with MPTP group,（Val8） GLP-1-Glu-PAL could statistically improved the behavior deficit,the swimming score （1.120±0.143） and dropping latency（20.546±7.823） in the MPTP＋Val8 group,and differences were statistically significant （P〈0.05）.Meanwhile,the TH positive neurons were significantly elevated （P〈0.01）.Conclusion The results suggest that （Val8）GLP-1-Glu-PAL has protective effects for MPTP induced mice PD dopaminergic neurons.
出处
《中华行为医学与脑科学杂志》
CAS
CSCD
北大核心
2014年第12期1068-1071,共4页
Chinese Journal of Behavioral Medicine and Brain Science
基金
山西省回国留学人员科研资助项目（2011-44）
