脂多糖对肠道α-突触核蛋白表达的影响

doi:10.3969/j.issn.1006-7795.2018.04.015

首都医科大学学报 ›› 2018, Vol. 39 ›› Issue (4): 557-562.doi: 10.3969/j.issn.1006-7795.2018.04.015

脂多糖对肠道α-突触核蛋白表达的影响

刘梦茹^1,2, 宫晓丽^2,3, 王乐^1,2, 刘玚^1,2, 张婷^1,2, 王晓民^1,2

1. 首都医科大学基础医学院神经生物学系, 北京 100069;
2. 首都医科大学教育部神经变性病重点实验室, 北京 100069;
3, 首都医科大学基础医学院生理与病理生理学系, 北京 100069

收稿日期:2018-05-21 出版日期:2018-07-21 发布日期:2018-07-21
通讯作者: 王晓民, 张婷 E-mail:wangwang.star@163.com;bugzt@sina.com
基金资助:
国家重点研究和发展计划（2016YFC1306300），国家自然科学基金重大项目资助（81527901），北京市自然科学基金（7162019），北京市科学技术委员会国家重大研发计划（Z161100002616007）。

Effect of lipopolysaccharide on the expression of α-synuclein in the intestinal tract

Liu Mengru^1,2, Gong Xiaoli^2,3, Wang Le^1,2, Liu Yang^1,2, Zhang Ting^1,2, Wang Xiaomin^1,2

1. Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China;
2. Key Laboratory of Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, China;
3. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China

Received:2018-05-21 Online:2018-07-21 Published:2018-07-21
Supported by:
This study was supported by National Key Research and Development Program (2016YFC1306300), Major Program of the National Natural Science Foundation of China (81527901), Natural Science Foundation of Beijing (7162019),National Major Research and Development Program of Beijing Municipal Science & Technology Commission (Z161100002616007).

摘要/Abstract

摘要： 目的腹腔注射细菌脂多糖（lipopolysaccharide，LPS）构建炎性反应诱导的帕金森病（Parkinson's disease，PD）小鼠模型，检测PD模型小鼠的结肠中α-突触核蛋白（α-synuclein，α-syn）的表达情况，以及结肠组织的炎性反应水平，探索炎性反应对PD早期外周结肠组织中关键致病蛋白α-syn表达的影响。方法将雄性的C57BL/6J小鼠采用数字表法随机分为0.9%（质量分数）氯化钠注射液对照组和模型组，给予小鼠单次腹腔注射5 mg/kg LPS或等体积0.9%（质量分数）氯化钠注射液，通过检测外周血中肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）的含量和小鼠体质量来评价模型建立情况；通过蛋白免疫印迹检测结肠组织α-突触核蛋白（α-synuclein，α-syn）的表达和炎性反应小体的激活情况；通过反转录-聚合酶链反应（reverse transcription-polymerase chain reaction，RT-qPCR）检测结肠组织炎性反应因子TNF-α的转录水平。结果 LPS注射后急性期（3 h内），小鼠结肠α-syn蛋白表达增加，并伴随炎性反应小体NOD样受体家族蛋白3（NOD-like receptor protein 3，NLRP3）蛋白和TNF-α mRNA的表达增加；LPS注射后慢性期（1个月），小鼠结肠α-syn及NLRP3蛋白表达恢复正常水平，但结肠的炎性反应因子TNF-α较对照组仍明显增加。结论 LPS可以促进α-syn在结肠内的表达，并伴随着结肠组织炎性反应小体激活和炎性反应因子TNF-α的表达，一个月时α-syn和炎性反应小体NLRP3恢复至正常水平，但结肠炎性反应因子TNF-α的持续高表达，很可能是导致LPS诱导的PD模型慢性反应期α-syn蛋白再一次持续升高的原因。

关键词: α-突触核蛋白, 炎性反应, 肠道, 帕金森病

Abstract: Objective Intraperitoneal injection of lipopolysaccharide (LPS) was used to construct Parkinson's disease (PD) mouse model. The protein level of α-synuclein (α-syn) and intestinal inflammation were detected in intestinal tissue of PD mice, to explore the expression of key pathogenic protein in the intestinal tract of early PD. Methods Male C57BL/6J mice were divided into control group and model group, mice received intraperitoneal injection of LPS or 0.9% saline. The mice model was characterized by detecting the level of inflammatory factor tumor necrosis factor-α(TNF-α) in blood and body weight. The protein level of α-synuclein(α-syn) and inflammasome NOD-like receptor protein 3 (NLRP3) in intestine were detected by Western blotting, the expression of TNF-α was measured by reverse transcription-polymerase chain reaction (RT-qPCR). Results In the acute phase, the expression of α-syn, NLRP3 and TNF-α were increased after LPS injection, the α-syn and NLRP3 returned to baseline levels at one month after LPS administration. But the expression of TNF-α was still at a high level. Conclusion LPS promoted the expression of α-syn in the intestine, which was accompanied by inflammasome activation and TNF-α expression. However, the high level of TNF-α is likely to lead to the progressive increase of α-syn in the chronic period of PD model induced by LPS.

Key words: α-synuclein, inflammation, intestine, Parkinson's disease

中图分类号:

R741.02

刘梦茹, 宫晓丽, 王乐, 刘玚, 张婷, 王晓民. 脂多糖对肠道α-突触核蛋白表达的影响[J]. 首都医科大学学报, 2018, 39(4): 557-562.

Liu Mengru, Gong Xiaoli, Wang Le, Liu Yang, Zhang Ting, Wang Xiaomin. Effect of lipopolysaccharide on the expression of α-synuclein in the intestinal tract[J]. Journal of Capital Medical University, 2018, 39(4): 557-562.

参考文献

[1] Hawkes C H, Del Tredici K, Braak H. A timeline for parkinson's disease[J]. Parkinsonism Relat Disord, 2010, 16(2):79-84.
[2] Barnum C J, Tansey M G. Neuroinflammation and non-motor symptoms:the dark passenger of Parkinson's disease?[J]. Curr Neurol Neurosci Rep, 2012, 12(4):350-358.
[3] Shannon K M, Keshavarzian A, Mutlu E, et al. Alpha-synuclein in colonic submucosa in early untreated Parkinson's disease[J]. Mov Disord,2012, 27(6):709-715.
[4] Wang L, Magen I, Yuan P Q, et al. Mice overexpressing wild-type human alpha-synuclein display alterations in colonic myenteric ganglia and defecation[J]. Neurogastroenterol Motil, 2012, 24(9):e425-e436.
[5] Klingelhoefer L, Reichmann H. Pathogenesis of parkinson disease-the gut-brain axis and environmental factors[J]. Nat Rev Neurol, 2015, 11(11):625-636.
[6] Kalia L V, Lang A E. Parkinson's disease[J]. Lancet, 2015, 386(9996):896-912.
[7] Hawkes C H, Del T K, Braak H. A timeline for parkinson's disease[J]. Parkinsonism Relat Disord, 2010, 16(2):79-84.
[8] Burré J, Sharma M, Südhof T C. Cell Biology and pathophysiology of α-Synuclein[J]. Cold Spring Harbor Perspect Med,2018, 8(3):a24091.
[9] Goedert M, Spillantini M G, Del Tredici K, et al. 100 years of Lewy pathology[J]. Nat Rev Neurol, 2013, 9(1):13-24.
[10] Cersosimo M G, Raina G B, Pecci C, et al. Gastrointestinal manifestations in Parkinson's disease:prevalence and occurrence before motor symptoms[J]. J Neurol, 2013,260(5):1332-1338.
[11] Chaudhuri K R, Martinez-Martin P, Schapira A H, et al. International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson's disease:the NMSQuest study[J]. Mov Disord, 2006, 21(7):916-923.
[12] Edwards L L, Pfeiffer R F, Quigley E M, et al. Gastrointestinal symptoms in parkinson's disease[J]. Mov Disord,1991, 6(2):151-156.
[13] Forsyth C B, Shannon K M, Kordower J H, et al. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease[J]. PLoS One, 2011, 6(12):e28032.
[14] Kelly L P, Carvey P M, Keshavarzian A, et al. Progression of intestinal permeability changes and alpha-synuclein expression in a mouse model of parkinson's disease[J]. Mov Disord, 2014, 29(8):999-1009.
[15] Qin L, Wu X, Block M L, et al. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration[J]. Glia, 2007, 55(5):453-462.

脂多糖对肠道α-突触核蛋白表达的影响

Effect of lipopolysaccharide on the expression of α-synuclein in the intestinal tract

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	王华, 史婷婷, 信中, 华琳, 李聪, 曹秋梅. Graves病患者促甲状腺素受体抗体与肠道菌群及短链脂肪酸的相关性[J]. 首都医科大学学报, 2022, 43(6): 931-939.
[2]	安宇, 边南南, 丁小雨, 常晓娜, 刘佳, 王广. 1型糖尿病伴认知功能损伤小鼠脑组织肠道菌群代谢物的改变[J]. 首都医科大学学报, 2022, 43(4): 622-629.
[3]	邵琳琳, 朱思莹, 邢洁, 武珊珊, 朱圣韬, 张澍田. 原发性胃肠道淋巴瘤的临床特征和内镜特点分析[J]. 首都医科大学学报, 2022, 43(2): 205-209.
[4]	粟文婷, 於佳楠, 贾军, 王晓民. 电针对帕金森病模型小鼠纹状体背侧的c-Fos表达的选择性调节[J]. 首都医科大学学报, 2021, 42(6): 986-992.
[5]	陈溪, 马登磊, 李林. 淫羊藿苷对cuprizone诱导精神分裂症样小鼠模型行为学变化、髓鞘脱失及神经炎性反应的影响[J]. 首都医科大学学报, 2021, 42(5): 761-767.
[6]	高歌, 查旭, 刘伟进, 杨慧. 129位丝氨酸磷酸化α-突触核蛋白DELFIA检测方法的建立及初步应用[J]. 首都医科大学学报, 2021, 42(5): 776-782.
[7]	王梦月, 赵鑫, 曹枭, 王可, 贾军. 帕金森病小鼠模型自主活动状态下的运动启动分析[J]. 首都医科大学学报, 2021, 42(4): 553-558.
[8]	张心红, 杨楚琪, 王轩, 沈霞光, 房纯, 王凤英. 白细胞介素-6和超敏C反应蛋白与围产期颅内静脉窦血栓的相关性研究[J]. 首都医科大学学报, 2021, 42(2): 210-213.
[9]	袁惠莉, 宫晓丽, 范征, 梁志刚, 王晓民. 远志皂苷对脂多糖诱导的帕金森病模型大鼠的作用及机制研究[J]. 首都医科大学学报, 2020, 41(6): 914-922.
[10]	宋启晗, 李旭冉, 李昕, 杨巍巍, 李伟, 于顺. 不同亚型的帕金森病及多系统萎缩患者血浆α-突触核蛋白寡聚体浓度分析[J]. 首都医科大学学报, 2020, 41(2): 212-216.
[11]	马超, 贺毅, 孙作厘, 刘鑫垚, 冯正田, 陈沛, 宁艳哲, 朱虹, 尹冬青, 贾竑晓. 基于16S rRNA技术分析石珍安神汤对脱髓鞘小鼠肠道菌群多样性的影响[J]. 首都医科大学学报, 2020, 41(1): 64-70.
[12]	刘萍, 娄可, 文隆, 李慧, 汤渝玲. 氧化应激介导NLRP3炎性反应小体对慢性阻塞性肺疾病的影响研究[J]. 首都医科大学学报, 2020, 41(1): 131-136.
[13]	王田田, 高琛琛, 李利生, 徐敬东. 消化道巨噬细胞的功能与炎性肠病和肠道肿瘤的相关性研究进展[J]. 首都医科大学学报, 2019, 40(6): 972-981.
[14]	丁晖, 蔡彦宁, 陈彪. 灵芝提取物对MPP⁺诱导的Neuro-2a细胞自噬的影响[J]. 首都医科大学学报, 2019, 40(4): 596-601.
[15]	刘欣, 张广中, 姜春燕, 肖士菊, 谭勇, 曲剑华, 陈妍霏. 肠道微生态与银屑病的中医研究[J]. 首都医科大学学报, 2019, 40(3): 363-368.