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5-羟色胺和肠道菌群在铅暴露诱导大鼠抑郁样行为中的作用

Role of 5-Hydroxytryptamine and Intestinal Flora on Depressive-Like Behavior Induced by Lead Exposure in Rats.

作者信息

Chen Xiaojun, Meng Shujuan, Li Shuang, Zhang Lijin, Wu Lei, Zhu Hao, Zhang Yanshu

机构信息

School of Public Health, North China University of Science and Technology, Hebei, China.

Workers' Hospital of Caofeidian District, China.

出版信息

Biomed Res Int. 2021 Apr 30;2021:5516604. doi: 10.1155/2021/5516604. eCollection 2021.

Abstract

OBJECTIVE

To investigate the effects of 5-hydroxytryptamine (5-HT) and intestinal flora on depression-like behavior induced by lead exposure in rats.

METHODS

30 healthy SPF adult male SD rats were randomly divided into control group and lead exposure group. The depression-like behavior of rats was detected. The blood, striatum, and intestinal tissue were collected. The lead content was detected by ICP-MS. The mRNA expressions of ChgA, TPH1, 5-HT, and 5-HT3R were tested by qRT-PCR. The content of 5HT was checked by HPLC-ECD. The content of 5-HT3R was detected by ELISA. The protein expressions of 5-HT, 5-HT3R, ChgA, and TPH were gauged by immunohistochemistry. Fecal samples were collected, and the composition of intestinal flora in experimental rats was analyzed by 16 s RNA metagene sequencing.

RESULTS

Lead exposure can greatly cause depression. The content of 5-HT in blood and striatum in the lead exposure group decreased, and the expression levels of 5-HT, 5-HT3 R, ChgA, and TPH in the intestine decreased distinctly. Compared with the control group, the distribution of a-polymorphism related indexes Simpson, Chao1, Shannon, and ACE in rats with depressive-like behavior after lead exposure was significantly increased; in the lead exposure group, there were 61 different operational taxonomic units (OUTs) in intestinal flora at the family level. Based on linear discriminant analysis, it was found that the key bacteria were Lactobacillaceae and Bifidobacteriaceae, and their abundance decreased evidently in the lead exposure group.

CONCLUSION

Lead exposure improves depressive-like behavior by affecting intestinal flora and regulating neurotransmitter 5-HT through the intestinal-brain axis.

摘要

目的

探讨5-羟色胺(5-HT)及肠道菌群对铅暴露诱导大鼠抑郁样行为的影响。

方法

将30只健康SPF成年雄性SD大鼠随机分为对照组和铅暴露组。检测大鼠的抑郁样行为。采集血液、纹状体及肠道组织。采用电感耦合等离子体质谱法检测铅含量。通过qRT-PCR检测ChgA、TPH1、5-HT及5-HT3R的mRNA表达。采用高效液相色谱-电化学检测法检测5HT含量。采用酶联免疫吸附测定法检测5-HT3R含量。通过免疫组织化学法检测5-HT、5-HT3R、ChgA及TPH的蛋白表达。收集粪便样本,采用16s RNA宏基因测序分析实验大鼠肠道菌群的组成。

结果

铅暴露可显著导致抑郁。铅暴露组血液和纹状体中5-HT含量降低,肠道中5-HT、5-HT3R、ChgA及TPH的表达水平明显下降。与对照组相比,铅暴露后出现抑郁样行为的大鼠中,与α-多样性相关的指数Simpson、Chao1、Shannon及ACE的分布显著增加;在铅暴露组中,肠道菌群在科级水平上有61个不同的可操作分类单元(OUTs)。基于线性判别分析,发现关键细菌为乳杆菌科和双歧杆菌科,其丰度在铅暴露组中明显降低。

结论

铅暴露通过影响肠道菌群并通过肠-脑轴调节神经递质5-HT来改善抑郁样行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0ea/8110379/bb80c40dba73/BMRI2021-5516604.001.jpg

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