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Restraint Stress in Hypertensive Rats Activates the Intestinal Macrophages and Reduces Intestinal Barrier Accompanied by Intestinal Flora Dysbiosis

Authors Wang T, Gao L, Yang Z, Wang F, Guo Y, Wang B, Hua R, Shang H, Xu J

Received 22 December 2020

Accepted for publication 22 February 2021

Published 25 March 2021 Volume 2021:14 Pages 1085—1110


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor Ning Quan

Tiantian Wang,1 Lei Gao,2 Zejun Yang,3 Feifei Wang,3 Yuexin Guo,4 Boya Wang,5 Rongxuan Hua,3 Hongwei Shang,6 Jingdong Xu1

1Department of Physiology and Pathophysiology, Basic Medical College, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Department of Biomedical Informatics, School of Biomedical Engineering, Capital Medical University, Beijing, 100069, People’s Republic of China; 3Department of Clinical Medicine, Basic Medical College, Capital Medical University, Beijing, 100069, People’s Republic of China; 4Department of Oral Medicine, Basic Medical College, Capital Medical University, Beijing, 100069, People’s Republic of China; 5Eight Program of Clinical Medicine, Peking University Health Science Center, Beijing, 100081, People’s Republic of China; 6Experimental Center for Morphological Research Platform, Capital Medical University, Beijing, 100069, People’s Republic of China

Correspondence: Jingdong Xu Tel +86-10-83911469
Email [email protected]

Purpose: Hypertension (HTN) is a major risk factor for cardiovascular disease. In recent years, there were numerous studies on the function of stress in HTN. However, the gut dysbiosis linked to hypertension in animal models under stress is still incompletely understood. Purpose of this study is to use multiple determination method to determine the juvenile stage intestinal bacteria, cytokines and changes in hormone levels.
Methods: Four groups of juvenile male spontaneously hypertensive rats (SHRs) and age-matched male Wistar-Kyoto (WKY) rats were randomly selected as control and experimental groups. Rats in the two stress groups were exposed to restraint stress for 3 hours per day for 7 consecutive days. In one day three times in the method of non-invasive type tail-cuff monitoring blood pressure. The detailed mechanism was illuminated based on the intestinal change using immunohistochemical and immunofluorescence staining and the stress-related hormone and inflammation factors were analyzed via ELISA method. The integrity of the epithelial barrier was assessed using FITC/HRP and the expression levels of proteins associated with the tight junction was detected by Western blot. The alteration of stress-related intestinal flora from ileocecal junction and distal colon were also analyzed using its 16S rDNA sequencing.
Results: The results indicate that acute stress rapidly increases mean arterial pressure which is positive correlation to hormone concentration, especially in SHR-stress group. Meanwhile, stress promoted the enhancement of epithelial permeability accompanied with a reduced expression of the tight junction-related protein and the macrophages (M&phis;) aggregation to the lamina propria. There were remarkable significant increase of stress-related hormones and pro-inflammatory factor interleukin (IL)-6 along with a decrease in the diversity of intestinal flora and an imbalance in the F/B ratio.
Conclusion: Our results reveal that stress accompanied with HTN could significantly disrupt the domino effect between intestinal flora and homeostasis.

Keywords: hypertension, restraint stress, intestinal flora, juvenile rat, intestinal barrier, macrophages

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