青岛大学学报（医学版）2024，Vol.60Issue(4)：478-482,5.DOI:10.11712/jms.2096-5532.2024.60.093
CB2受体激活对慢性PD模型小鼠运动功能和黑质胶质细胞活化影响
Effect of cannabinoid type 2 receptor activation on motor function and glial cell activation in the substantia nigra in a mouse model of chronic Parkinson's disease
摘要
Abstract
Objective To investigate the effect of cannabinoid type 2(CB2)receptor on motor function,the protein expres-sion of tyrosine hydroxylase(TH),and the activation of microglial cells and astrocytes in the substantia nigra(SN)in a mouse model of chronic Parkinson's disease(PD)induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)based on beha-vioristics,Western blotting,and immunohistochemistry.Methods A total of 30 wild-type(WT)male C57BL/6 mice,aged 8 weeks,were randomly divided into WT control group(group A),WT MPTP group(group B),WT CB2 receptor agonist JWH133 group(group C),WT MPTP+JWH133 group(group D),and WT MPTP+JWH133+CB2 receptor antagonist AM630 group(group E),and 12 CB2 receptor-knockout(CB2-KO)male C57BL/6 mice were randomly divided into CB2-KO control group(group F)and CB2-KO MPTP group(group G).The mice in the model group were given intraperitoneal injection of 20 μg/(kg·d)AM630 and/or 10 μg/(kg·d)JWH133 once a day for 30 consecutive days,followed by intraperitoneal injection of 30 mg/(kg d)MPTP twice a week for four weeks,while those in the control group were given intraperitoneal injection ofan equal volume of normal saline.Behavioral experiments were used to measure the time of poleclimbing and the time spent on the rotating rod;Western blotting was used to measure the protein expression of TH in the SN;immunohistochemical staining was used to observe changes in the number and morphology of microglial cells and astrocytes in the SN.Results Compared with group A,group B had a significant increase in the time of poleclimbing and a significant reduc-tion in the time spent on the rotating rod;compared with group B,group D had a significant reduction in the time of poleclimbing and a significant increase in the time spent on the rotating rod;compared with group D,group E had a significant increase in the time of poleclimbing and a significant reduction in the time spent on the rotating rod;compared with group F,group D had a signi-ficant increase in the time of poleclimbing and a significant reduction in the time spent on the rotating rod(F=29.70,45.45;q=4.87-18.09;P＜0.05).Compared with group A,group B had a significant reduction in the protein expression level of TH in the SN of mice;compared with group B,group D had a significant increase in the protein expression level of TH;compared with group D,group E had a significant reduction in the protein expression level of TH;compared with group F,group G had a significant re-duction in the protein expression level of TH(F=24.88,q=5.09-8.88,P＜0.001).Compared with group A,group B had signifi-cant increases in the numbers of activated microglial cells and astrocytes in the SN of mice;compared with B,group D had signifi-cant reductions in these numbers;compared with group D,group E had significant increases in these numbers;compared with group F,group G had significant increases in these numbers(F=269.80,708.50;q=13.29-54.78;P＜0.01).Conclusion Ac-tivation of CB2 receptor can improve dyskinesia and inhibit the activation of microglial cells and astrocytes in the SN of mice with MPTP-induced chronic PD.关键词
受体,大麻酚,CB2/帕金森病/1-甲基-4-苯基吡啶/旋转棒性能试验/黑质/小神经胶质细胞/星形细胞/小鼠,近交C57BLKey words
receptor,cannabinoid,CB2/Parkinson disease/1-methyl-4-phenylpyridinium/rotarod performance test/sub-stantia nigra/microglia/astrocytes/mice,inbred C57BL分类
医药卫生引用本文复制引用
刘欣宇,张丽,马泽刚..CB2受体激活对慢性PD模型小鼠运动功能和黑质胶质细胞活化影响[J].青岛大学学报（医学版）,2024,60(4):478-482,5.基金项目
山东省重点研发计划资助项目(2019GSF10-8095) （2019GSF10-8095）
