新型肠促胰岛素双受体激动剂对亚急性帕金森病小鼠步态行为的影响及机制研究  

Effect of new incretin agonist on gait behavior of subacute PD mice and its mechanism

作　　者：吕妙君 冯鹏[2] 郭雅静 程慧峰 薛国芳[2] LV Miaojun;Feng Peng;Guo Yajing;Cheng Huifeng;Xue Guofang(Shanxi Medical University No.2 School of Clinical Medicine,Taiyuan 030000,Shanxi Province,China)

机构地区：[1]山西医科大学第二临床医学院,太原030000 [2]山西医科大学第二医院神经内科

出　　处：《中华老年心脑血管病杂志》2021年第9期908-912,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：山西省自然科学基金(201901D111383)。

摘　　要：目的研究新型胰高血糖素样肽1(GLP-1)/葡萄糖依赖性促胰岛素样肽双受体激动剂DA-CH5对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)所致亚急性帕金森病(PD)小鼠步态运动行为的影响,并对比分析其与GLP-1受体激动剂NLY01的效果。方法将48只雄性C57BL小鼠随机分为对照组、MPTP组、MPTP+DA-CH5组(联合1组)、MPTP+NLY01组(联合2组),每组12只。在PD建模第7天进行行为学测试,采用免疫组织化学染色观察小鼠脑组织黑质致密部酪氨酸羟化酶(TH)阳性细胞数。结果与对照组比较,MPTP组步态实验步幅、前爪摇摆时间百分比、后爪摇摆时间百分比、转棒实验掉落潜伏期、旷场实验总移动距离、中脑黑质区TH阳性细胞数、TH和Bcl-2表达明显降低,后爪步幅宽度、α突触核蛋白、Bax、Bax/Bcl-2比值明显升高,差异有统计学意义(P<0.01)。与MPTP组比较,联合1组和联合2组步态实验步幅、前爪摇摆时间百分比、后爪摇摆时间百分比、转棒实验掉落潜伏期、旷场实验总移动距离、TH阳性细胞数、TH及Bcl-2表达明显升高,联合1组后爪步幅宽度、α突触核蛋白、Bax、Bax/Bcl-2比值明显降低(P<0.01)。联合1组步态实验步幅、前爪摇摆时间百分比、后爪摇摆时间百分比、转棒实验掉落潜伏期、旷场实验总移动距离、TH阳性细胞数、TH、Bcl-2表达明显高于联合2组(P<0.05,P<0.01),后爪步幅宽度、α突触核蛋白、Bax、Bax/Bcl-2比值明显低于联合2组[(37.50±2.20)mm vs(44.99±1.58)mm,0.45±0.03 vs 0.97±0.02,0.70±0.03 vs 0.88±0.05,0.89±0.08 vs 1.36±0.11;P<0.05,P<0.01]。结论DA-CH5可抑制小鼠PD导致的步态行为学障碍,减少酪氨酸神经元丢失,具有神经保护作用,且效果优于NLY01。Objective To compare the effect of new GLP-1/GIP dual receptor agonist DA-CH5 and single receptor agonist NLY01 on the gait and motor behaviors in subacute PD mice.Methods Forty-eight male C57BL mice were randomly divided into control group,MPTP group,MPTP+DA-CH5 group,MPTP+NLY01 group(12 in each group).Their behaviors were tested on day 7 after PD modeling.The tyrosine hydroxylase(TH)positive cells in substantia nigra compact part of mice were detected with immunohistochemical staining.Results The stride length,percentage of swing time for forepaw and hindpaw in gait experiment,the latent period of rotor fall and total moving distance of open field test were significantly shorter,the number of TH posive cells in substantia nigra compact part of mice was significantly smaller,the stride width of hindpaw and the expression levels of TH and Bcl-2 were significantly higher while those ofα-synuclein,Bax and Bax/Bcl-2 were significantly lower in MPTP group than in control group(P<0.01),in MPTP+DA-CH5 group and MPTP+NLY01 group than in MPTP group(P<0.05,P<0.01),and in MPTP+DA-CH5 group than in MPTP+NLY01 group(37.50±2.20 mm vs 44.99±1.58 mm,0.45±0.03 vs 0.97±0.02,0.70±0.03 vs 0.88±0.05,0.89±0.08 vs 1.36±0.11,P<0.05,P<0.01).Conclusion DA-CH5 can inhibit PD-induced gait and behaviors in mice.The neuroprotective effect of DA-CH5 achieved by reducing the loss of tyrosine neurons and inhibiting the cell apoptosis is better than that of NLY01.

关 键 词：帕金森病 步态失调 肠促胰岛素类 胰高血糖素样肽1 肠抑胃肽 Α突触核蛋白 

分 类 号：R742.5[医药卫生—神经病学与精神病学]