鱼藤酮诱导帕金森病模型小鼠体内肠道微生物的变化

韩秋琴 万国庆 顾雪锋

解剖学报 ›› 2020, Vol. 51 ›› Issue (4) : 507-512.

PDF(2482 KB)
欢迎访问《解剖学报》官方网站!今天是 English
PDF(2482 KB)
解剖学报 ›› 2020, Vol. 51 ›› Issue (4) : 507-512. DOI: 10.16098/j.issn.0529-1356.2020.04.006
神经生物学

 鱼藤酮诱导帕金森病模型小鼠体内肠道微生物的变化

  • 韩秋琴 万国庆* 顾雪锋*
作者信息 +

Detection of intestinal microbial changes in rotenone-induced Parkinson’s disease model mice#br#

  • HAN Qiu-qin WAN Guo-qing* GU Xue-feng*
Author information +
文章历史 +

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。

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.

关键词

帕金森病 / 鱼藤酮 / 肠道微生物 / 16S rRNA / 旷场实验 / 小鼠

Key words

Parkinson’s disease / Rotenone / Intestinal microbe / 16S rRNA / Open field experiment / Mouse

引用本文

导出引用
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 https://doi.org/10.16098/j.issn.0529-1356.2020.04.006
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 https://doi.org/10.16098/j.issn.0529-1356.2020.04.006
中图分类号: R361+.1    

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.

基金

上海健康医学院种子基金;上海健康医学院师资人才百人库项目

PDF(2482 KB)

Accesses

Citation

Detail

段落导航
相关文章

/