胰高血糖素样肽-1蛋白对帕金森病氧化应激损伤的保护作用及机制研究

Protective effect and mechanism of GLP-1 protein on oxidative stress injury in Parkinson’s disease

目的:探讨胰高血糖素样肽-1(GLP-1)蛋白对帕金森病氧化应激损伤的保护作用及机制。方法:36只8周龄C57BL/6雄性小鼠随机平分为三组(模型组、利拉鲁肽组与GLP-1组)。所有小鼠都给予建立帕金森病模型,模型组在建模过程中给予0.1 ml 0.9%氯化钠溶液注射,利拉鲁肽组在给予利拉鲁肽腹腔注射25 nmol/(kg·d),GLP-1组在建给予GLP-1/GIP双受体激动剂(DA3-CH)腹腔注射25 nmol/(kg·d),连续治疗7 d。结果:三组建模第7天的转棒停留时间、牵拉肌张力评分都低于建模第1天(均P<0.05),利拉鲁肽组与GLP-1组高于模型组(P<0.05),GLP-1组高于利拉鲁肽组(均P<0.05)。利拉鲁肽组与GLP-1组建模第7天的血清Chi3l1含量、脑组织IBA-1和胶质纤维酸性蛋白(GFAP)相对表达水平低于模型组(均P<0.05),GLP-1组低于利拉鲁肽组(P<0.05)。结论:GLP-1蛋白在帕金森病小鼠的应用能缓解氧化应激损伤,抑制血清Chi3l1与脑组织IBA-1、GFAP蛋白的表达,从而发挥神经保护作用。

Objective:To explore the protective effect and mechanism of glucagon-like peptide-1(GLP-1)protein on oxidative stress injury in Parkinson’s disease.Methods:36 cases of 8-week-old C57BL/6 male mice were randomly divided into model group,liraglutide group and GLP-1 group.All mice were constructed of Parkinson’s disease model.The model group was injected with 0.1 ml of 0.9%sodium chloride solution during the modeling process,the liraglutide group was given intraperitoneal injection of 25 nmol/(kg·d)with liraglutide,and the GLP-1 group was given intraperitoneal injection of 25 nmol/(kg·d)of GLP-1/GIP dual receptor agonist(DA3-CH)for 7 consecutive days.Results:The rotor stay time and stretch muscle tension scores on the 7th day of the three groups of modeling were lower than those on the 1st day of modeling(all P<0.05),and the liraglutide group and GLP-1 group were higher than the model group(P<0.05),and the GLP-1 group were higher than the liraglutide group(all P<0.05).The serum Chi3l1 content and the relative expression levels of brain tissue IBA-1 and GFAP proteins of the liraglutide group and the GLP-1 group were lower than those of the model group on the 7th day of modeling(all P<0.05),and the GLP-1 group were lower than the liraglutide group(all P<0.05).Conclusion:The application of GLP-1 protein in Parkinson’s disease mice can alleviate oxidative stress damage and inhibit the expression of serum Chi3l1 and brain tissue IBA-1 and GFAP proteins,thereby exerting neuroprotective effects.