鱼藤酮诱导帕金森病模型小鼠体内肠道微生物的变化

doi:10.16098/j.issn.0529-1356.2020.04.006

摘要/Abstract

摘要：

目的基于16S rRNA基因测序，探讨鱼藤酮诱导的帕金森病(PD）模型小鼠体内肠道微生物的变化。方法 14只8周雄性C57BL/6J小鼠连续5周每天皮下注射鱼藤酮（3 mg/kg），每周测1次体重，5周后进行行为学检测，包括转棒实验和旷场实验，最后收集肠道内容物，用于肠道微生物检测分析。结果给鱼藤酮5周后，PD模型小鼠的体重显著低于对照小鼠（P<0.05），PD模型小鼠在转棒中的运动时间（P<0.0001）和在旷场中的运动总路程（P<0.05）均显著低于对照小鼠。PD模型小鼠肠道微生物Alpha多样性没有变化（P> 0.05），但是微生物物种与对照组间差异有显著性，其中PD模型小鼠肠道铜绿假单胞菌（Turicibacter）显著减少（P<0.01），毛螺旋菌科（norank_f_Lachnospiraceae）显著增多（P<0.01），丹毒丝菌科（norank_f_Erysipelotrichaceae）显著减少（P<0.01），腔隙杆菌属（Lachnoclostridium）显著增多（P<0.01）。

结论 PD模型小鼠的肠道微生物紊乱；肠道菌群紊乱可能参与PD模型小鼠运动障碍的发生。

关键词: 帕金森病, 鱼藤酮, 肠道微生物, 16S rRNA, 旷场实验, 小鼠

Abstract:

Objective To investigate the changes of intestinal microbes in rotenone-induced Parkinson’s disease (PD) mice based on 16S rRNA gene sequencing. Methods Fourteen 8-weekold male C57BL/6J mice were randomly divided into two groups: 6 mice in the control group and 8 mice in the model group. The model mice were injected subcutaneously with rotenone (3 mg/kg) for 5 weeks, and the body weight was measured once a week. After 5 weeks, behavioral tests were performed, including the rotating rod test and the open field test. The contents of the tract were used for intestinal microbial detection analysis. Results After 5 weeks of rotenone treatment, the weight of PD mice was significantly lower than that of the control mice（P<0.05）. The movement time of the PD model mice in the rotating rod（P<0.0001）and the total distance of movement in the open field（P<0.05）were significantly lower than that of the control mice. In addition, the intestinal microbial diversity of the PD model mice did not change（P>0.05）,but the microbial species showed significant differences. Among them, the PD mice showed a significant decrease in the intestinal Turicibacter（P<0.01）, a significant increase in norank_f_Lachnospiraceae（P<0.01）, a significant decrease in norank_f_ Erysipelotrichacea e（P<0.01）, and a significant increase in Lachnoclostridium（P<0.01）. Conclusion Intestinal microbes in PD mice are disordered, and these intestinal flora may be involved in the development of dyskinesia in PD mice.

Key words: Parkinson’s disease, Rotenone, Intestinal microbe, 16S rRNA, Open field experiment, Mouse

中图分类号:

R361⁺.1

韩秋琴万国庆顾雪锋. 鱼藤酮诱导帕金森病模型小鼠体内肠道微生物的变化[J]. 解剖学报, 2020, 51(4): 507-512.

HAN Qiu-qin WAN Guo-qing GU Xue-feng. Detection of intestinal microbial changes in rotenone-induced Parkinson’s disease model mice#br#[J]. Acta Anatomica Sinica, 2020, 51(4): 507-512.

参考文献

［1］ Hirsch L, Jette N, Frolkis A, et al. The incidence of Parkinson’s disease: a systematic review and meta analysis［J］. Neuroepidemiology, 2016,46(4):292-300.

［2］ Nalls MA, Pankratz N, Lill CM, et al. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease［J］. Nat Genet, 2014,46(9):989-993.

［3］ Greenamyre JT, Cannon JR, Drolet R, et al. Lessons from the rotenone model of Parkinson’s disease［J］. Trends Pharmacol Sci, 2010,31(4):141-143.

［4］ Mertsalmi TH, Aho Ⅴ, Pereira P, et al. More than constipation -bowel symptoms in Parkinson’s disease and their connection to gut microbiota［J］. Eur J Neurol, 2017,24(11):1375-1383.

［5］ Lai F, Jiang R, Xie W, et al. Intestinal pathology and gut microbiota alterations in a methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease［J］. Neurochem Res, 2018,43(10):1986-1999.

［6］ Khlevner J, Park Y, Margolis KG. Brain-gut axis: clinical implications［J］. Gastroenterol Clin North Am, 2018,47(4):727-739.

［7］ Al OY, Aziz Q. The brain-gut axis in health and disease［J］. Adv Exp Med Biol, 2014,817:135-153.

［8］ Wang S, Harvey L, Martin R, et al. Targeting the gut microbiota to influence brain development and function in early life［J］. Neurosci Biobehav Rev, 2018,95:191-201.

［9］ Radisavljevic N, Cirstea M, Brett F B. Bottoms up: the role of gut microbiota in brain health［J］. Environ Microbiol, 2019, 21(9):3197-3211.

［10］ Strandwitz P. Neurotransmitter modulation by the gut microbiota［J］. Brain Res, 2018,1693(Pt B):128-133.

［11］ Jameson KG, Hsiao EY. Linking the gut microbiota to a brain neurotransmitter［J］. Trends Neurosci, 2018,41(7):413-414.

［12］ Clark A, Mach N. Exercise-induced stress behavior, gut-microbiota-brain axis and diet: a systematic review for athletes［J］. J Int Soc Sports Nutr, 2016,13:43.

［13］ Szyszkowicz JK, Wong A, Anisman H, et al. Implications of the gut microbiota in vulnerability to the social avoidance effects of chronic social defeat in male mice［J］. Brain Behav Immun, 2017,66:45-55.

［14］ Allen JM, Berg MM, Pence BD, et al. Voluntary and forced exercise differentially alters the gut microbiome in C57BL/6J mice［J］. J Appl Physiol (1985), 2015,118(8):1059-1066.

［15］ Li F, Wang P, Chen Z, et al. Alteration of the fecal microbiota in North-Eastern Han Chinese population with sporadic Parkinson’s disease［J］. Neurosci Lett, 2019,707:134297.

［16］ Hugenholtz F, Davids M, Schwarz J, et al. Metatranscriptome analysis of the microbial fermentation of dietary milk proteins in the murine gut［J］. PLoS One, 2018,13(4):e194066.

［17］ Bedarf JR, Hildebrand F, Coelho LP, et al. Functional implications of microbial and viral gut metagenome changes in early stage L-DOPA-naive Parkinson’s disease patients［J］. Genome Med, 2017,9(1):39.

［18］ Ren ShM, Mei L, Huang H, et al. Correlation analysis of gut microbiota and biochemical indexes in patients with non-alcoholic fatty liver disease ［J］. Chinese Journal of Hepatology, 2019,27(5):369-375.(in Chinese)

任士萌，梅璐，黄煌，等.非酒精性脂肪性肝病患者肠道菌群及生物化学指标相关性分析［J］.中华肝脏病杂志，2019，27(5):369-375.

［19］ Wang Z, Wang Q, Zhao J, et al. Altered diversity and composition of the gut microbiome in patients with cervical cancer［J］. AMB Express, 2019,9(1):40.

［20］ Sampson TR, Debelius JW, Thron T, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease［J］. Cell, 2016,167(6):1469-1480.

［21］ Li W, Wu X, Hu X, et al. Structural changes of gut microbiota in Parkinson’s disease and its correlation with clinical features［J］. Sci China Life Sci, 2017,60(11):1223-1233.

［22］ Lin A, Zheng W, He Y, et al. Gut microbiota in patients with Parkinson’s disease in southern China［J］. Parkinsonism Relat Disord, 2018,53:82-88.

［23］ Petrov VA, Saltykova Ⅳ, Zhukova IA, et al. Analysis of gut microbiota in patients with Parkinson’s disease［J］. Bull Exp Biol Med, 2017,162(6):734-737.

［24］ Sun MF, Zhu YL, Zhou ZL, et al. Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson’s disease mice: Gut microbiota, glial reaction and TLR4/TNF-alpha signaling pathway［J］. Brain Behav Immun, 2018,70:48-60.

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