童巧文　　陈杨芳　　林建萍　　冯梅　　叶华

结果 从属水平上看，HC组相对于PD组，毛螺旋菌、链球菌属、克雷伯菌属、伯劳特菌属4种属显著增加（P<0.05）。PD组相对于HC组，有埃希氏菌属、瘤胃球菌属、巨单胞菌属、阿克曼氏菌属、巨型球菌属、颤杆菌克属、伯克氏菌属、埃森博格拉属、异味杆菌属、丹毒丝菌科未命名属、脱硫弧菌属、普雷沃氏菌科、单胞菌属、脱硫弧菌科、嗜胨菌属明显增加（P<0.05）。PD组血清TNF-α水平为101.56（46.30，200.62），高于对照组血清TNF-α水平83.53（37.72， 191.27），差异有统计学意义（P<0.05）;两组血清IL-6，LPS水平，差异无统计学意义（P>0.05）。TNF-α、IL-6、LPS与脱硫化弧菌属（Desulfovibrio）有正相关（P<0.05），IL-6、LPS与丹毒丝菌科未命名属（Erysipelotrichaceae incertae sedis）有正相关（P<0.05），IL-6、LPS与伯劳特菌属（Blautia）有正相关（相关系数为P<0.05）。 结论 帕金森病组和健康对照组的菌群结构存在有差异。PD肠道菌群中条件致病菌增多，并与细胞因子有一定相关。这些改变可能与帕金森病的发病机制有关。

[关键词] 帕金森病;肠道菌群;炎症因子;相关性分析

[中图分类号] R742.5           [文獻标识码] A          [文章编号] 1673-9701（2021）14-0012-04

Correlation analysis on intestinal flora and serum inflammatory factors in the patients with Parkinson′s disease

TONG Qiaowen1   CHEN Yangfang2   LIN Jianping2   FENG Mei1   YE Hua1

1.Department of Neurology， Wenzhou People′s Hospital， Wenzhou   325000， China; 2.Clinical Laboratory， Wenzhou People′s Hospital， Wenzhou   325000， China

[Abstract] Objective To analyze the correlation between changes of intestinal flora and serum inflammatory factors in the patients with Parkinson′s disease（PD）. Methods A total of 30 patients with primary PD who were admitted to the Department of Neurology in Wenzhou People′s Hospital from November 2017 to February 2019 and 30 patients undergoing routine physical examination during the same period were selected. After grouping， the general information was collected， and the blood and stool samples were collected. The types of microorganisms was determined through 16S-rRNA sequencing and the classification analysis of microorganisms was performed. The serum lipopolysaccharide （LPS）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） were detected. Correlation  Analysis was carried out between different flora abundance and serum inflammatory factors in PD. Results From the genus level， compared with the PD group， the HC group had significant increases in four genera： Lachnospira， Streptococcus， Klebsiella， and Blautia（P<0.05）. Compared with the HC group， the PD group had significant increases in Escherichia， Ruminococcus， Megamonas， Akkermansia， Megacoccus， Oscillibacter， Burkholderia， Erysipelotrichaceae incertae sedis， Desulfovibrio， Desulfovibrio， Desulfovibrio， and Peptoniphilus （P<0.05）. The serum TNF-α level in the PD group was 101.56 （46.30， 200.62）， which was higher than the serum TNF-α level of 83.53（37.72， 191.27） in the control group， and the difference was statistically significant（P<0.05）. There was no statistical difference in the levels of serum IL-6 and LPS between the two groups（P>0.05）. TNF-α， IL-6， and LPS were positively correlated with Desulfovibrio（P<0.05）， IL-6， LPS were positively correlated with Erysipelotrichaceae incertae sedis（P<0.05）， and IL-6 and LPS were positively correlated with Blautia （P<0.05）. Conclusion There are differences in the structure of the flora between the Parkinson′s disease group and the healthy control group. The increase in the intestinal flora of conditional pathogenic bacteria of PD is related to cytokines. These changes may be related to the pathogenesis of Parkinson′s disease.

[Key words] Parkinson′s disease （PD）; Intestinal flora; Inflammatory factors; Correlation analysis

帕金森病（Parkinson′s disease，PD）是一种中老年人常见的中枢神经系统退行性疾病。它的病理的特征在于α-突触核蛋白异常聚积，并影响脑-肠轴各级组织，包括中枢神经系统、自主神经系统和肠神经系统。最近一项涉及新诊断的PD患者的研究证实，与健康对照组相比，这些受试者的肠道通透性显著增加，这与肠黏膜中大肠杆菌的更强染色和全面暴露于血清脂多糖（Lipopolysaccharide，LPS）有关[1]。值得注意的是，这些改变也与肠道神经元中α-突触核蛋白的异常积聚有相关性[2]。越来越多的证据证实肠道菌群的改变先于或发生在PD过程中[3，4]。与肠道菌群的改变相关的肠道炎症可能促使α-突触核蛋白时错误折叠的发生[5，6]。

本研究通过16S-rDNA测序确定PD肠道菌群种类并进行微生物的分类分析，深入研究PD患者的肠道菌群结构的多样性特征，并应用酶联免疫法检测血清LPS，白细胞介素-6（Interleukin-6，IL-6）、肿瘤坏死因子-α（Tumor necrosis factor-α，TNF-α），以探索PD腸道菌群与炎症反应的相关性。

1 资料与方法

1.1 一般资料

研究对象及分组：本研究对象主要分为帕金森病例组（PD组）与健康对照组（HC组）。来自2017年11月至2019年2月在温州市人民医院门诊和住院诊治原发性PD的患者30例。PD组中男女比例为14∶16，平均年龄（66.5±7.4）岁。同时选择温州市人民医院体检中心30例年龄、性别匹配的健康志愿者作为健康对照组（HC组）。……