[1]刘 斌,杨浩辉,任 伯,等.丁苯酞联合美多芭对帕金森病伴抑郁模型小鼠黑质纹状体Ⅱ型髓系细胞触发受体及小胶质细胞炎症标志物表达的影响[J].陕西医学杂志,2022,51(12):1477-1482.[doi:DOI:10.3969/j.issn.1000-7377.2022.12.003]
　LIU Bin,YANG Haohui,REN Bo,et al.Effects of butylphthalide combined with medoba on expression of TREM2 and microglia inflammatory markers in substantia nigra striatum of Parkinson's disease with depression model mice[J].,2022,51(12):1477-1482.[doi:DOI:10.3969/j.issn.1000-7377.2022.12.003]
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丁苯酞联合美多芭对帕金森病伴抑郁模型小鼠黑质纹状体Ⅱ型髓系细胞触发受体及小胶质细胞炎症标志物表达的影响
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
51
期数:
2022年12期
页码:
1477-1482
栏目:
基础研究
出版日期:
2022-12-05

文章信息/Info

Title:
Effects of butylphthalide combined with medoba on expression of TREM2 and microglia inflammatory markers in substantia nigra striatum of Parkinson's disease with depression model mice
作者:
刘 斌; 杨浩辉; 任 伯; 范少凯; 毛文静; 王雅楠; 吴小坤
(华北理工大学附属医院神经内一科,河北 唐山 063000)
Author(s):
LIU Bin; YANG Haohui; REN Bo; FAN Shaokai; MAO Wenjing; WANG Yanan; WU Xiaokun
(First Department of Neurology,the Affiliated Hospital of North China University of Science and Technology,Tangshan 063000,China)
关键词:
帕金森病;  抑郁;  丁苯酞;  美多芭;  Ⅱ型髓系细胞触发受体;  小胶质细胞
Keywords:
Parkinson's disease;  Depression;  Butylphthalide;  Medoba;  TREM2;  Microglia
分类号:
R 742.5
DOI:
DOI:10.3969/j.issn.1000-7377.2022.12.003
文献标志码:
A
摘要:
目的:探讨丁苯酞联合美多芭对帕金森病伴抑郁模型小鼠黑质纹状体Ⅱ型髓系细胞触发受体(TREM2)及小胶质细胞M1型炎症标志物[白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)]及M2型炎症标志物[IL-10和精氨酸酶-1(Arg-1)]表达的影响。方法:随机将40只C57BL/6成年雄性小鼠分正常对照组(对照组)、帕金森病伴抑郁模型组(模型组)、美多芭治疗组和丁苯酞联合美多芭治疗组,每组10只。腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP,30 mg/kg×7 d)制备帕金森病小鼠模型。建立帕金森病模型后,以慢性不可预知温和应激诱导产生帕金森病伴抑郁小鼠模型。美多芭治疗组给予美多芭6.25 mg/kg灌胃治疗,1次/d,持续7 d。丁苯酞联合美多芭治疗组给予丁苯酞120 mg/kg和美多芭6.25 mg/kg灌胃治疗,1次/d,持续7 d。采用免疫组化定性分析黑质纹状体内α-突触核蛋白的阳性表达情况。采用酶联免疫吸附(ELISA)法测定5-羟色胺(5-HT)含量。采用蛋白免疫印迹法检测TREM2蛋白表达水平。采用蛋白免疫印迹和PCR检测小胶质细胞炎症标志物IL-1β、TNF-α、IL-10、Arg-1蛋白及mRNA表达水平。结果:模型组小鼠黑质纹状体部位可见大量α-突触核蛋白异常积聚; 美多芭治疗组及丁苯酞联合美多芭治疗组α-突触核蛋白阳性表达明显减少,染色变浅,以丁苯酞联合美多芭治疗组减少更明显。与对照组比较,模型组5-HT含量明显减低(P<0.05); 与模型组比较,美多芭治疗组及丁苯酞联合美多芭治疗组5-HT含量明显增加,以丁苯酞联合美多芭治疗组增加更明显(均P<0.05)。与对照组比较,模型组TREM2明显减低(P<0.05); 与模型组比较,美多芭治疗组及丁苯酞联合美多芭治疗组TREM2明显增加,以丁苯酞联合美多芭治疗组增加更明显(均P<0.05)。与对照组比较,模型组小胶质细胞M1型炎症标志物IL-1β和TNF-α明显升高,M2型标炎症标志物IL-10和Arg-1明显下降(均P<0.05); 与模型组比较,美多芭治疗组及丁苯酞联合美多芭治疗组IL-1β和TNF-α下降, IL-10和Arg-1增加,以丁苯酞联合美多芭治疗组更明显(均P<0.05)。结论:丁苯酞联合美多芭能促进帕金森病伴抑郁模型小鼠黑质纹状体TREM2表达增加,抑制炎症反应,对神经元具有保护作用。
Abstract:
Objective:To explore the effects of butylphthalide combined with medoba on TREM2 and microglia M1 marker IL-1β,TNF-α and M2 marker IL-10,Arg-1 in substantia nigra striatum of Parkinson's disease with depression model mice.Methods:Forty C57BL/6 adult male mice were randomly divided into normal control group(control group),Parkinson's disease with depression model group(model group),medoba treatment group and butylphthalide combined with medoba treatment group,with 10 mice in each group.The mouse model of Parkinson's disease was prepared by intraperitoneal injection of MPTP(30 mg/kg×7 d).After the establishment of Parkinson's disease model,the mouse model of Parkinson's disease with depression was induced by chronic unpredictable mild stress.The medoba treatment group was given medoba 6.25 mg/kg by gavage once a day for 7 days.The butylphthalide combined with medoba treatment group was given medoba 6.25 mg/kg and butylphthalide 120 mg/kg by gavage once a day for 7 days.The positive expression of α-synuclein in substantia nigra striatum was qualitatively analyzed by immunohistochemistry,and the content of serotonin was determined by enzyme-linked immunosorbent assay(ELISA),and the level of TREM2 protein in substantia nigra striatum was detected by Western blot,and microglia inflammatory markers IL-1β,TNF-α,IL-10,Arg-1 level changes of microglia were detected by Western blot and PCR.Results:A large number of α-synuclein abnormal accumulation in the model group were found in the substantia nigra and striatum,the positive expression of α-synuclein decreased significantly and the staining became lighter in medoba treatment group and butylphthalide combined with medoba treatment group,especially in butylphthalide combined with medoba treatment group.In comparison with the control group,5-HT content in the model group decreased significantly(P<0.05); in comparison with the model group,5-HT content increased significantly in medoba treatment group and butylphthalide combined with medoba treatment group,especially in butylphthalide combined with medoba treatment group(all P<0.05).In comparison with the control group,TREM2 expression in the model group decreased significantly(P<0.05); in comparison with the model group,TREM2 expression in medoba treatment group and butylphthalide combined with medoba treatment group increased significantly,especially in butylphthalide combined with medoba treatment group(all P<0.05).In comparison with the control group,the expression of IL-1β and TNF-α in the model group increased significantly,and the expression of IL-10 and Arg-1 decreased significantly(all P<0.05); in comparison with the model group,the expression of IL-1β and TNF-α in medoba treatment group and butylphthalide combined with medoba treatment group decreased,and the expression of IL-10 and Arg-1 increased,especially in butylphthalide combined with medoba treatment group(all P<0.05).Conclusion:Butylphthalide combined with medoba can increase the expression of TREM2 in substantia nigra striatum in Parkinson's disease with depression model mice,and inhibit inflammatory response,which has a protective effect on neurons.

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备注/Memo

备注/Memo:
基金项目:河北省政府资助临床医学优秀人才培养项目(2019046)
更新日期/Last Update: 2022-12-05