肾素血管紧张素系统在溃疡性结肠炎小鼠肠-血屏障损伤中的调控作用

doi:10.11843/j.issn.0366-6964.2024.04.037

Abstract

Abstract: The purpose of this study was to investigate the role of renin-angiotensin system (RAS) in gut-vascular barrier injury in ulcerative colitis mice. Sixteen ICR mice were selected and randomly divided into control and DSS groups by equal volume saline gavage. Mice in the DSS group were supplemented with DSS (final concentration of 4%) in the drinking water starting on day 4 of the study to establish a murine ulcerative colitis model. During this period, body weight, fecal characteristics, and fecal occult blood of the mice were recorded daily for the calculation of DAI. Until day 8 of DSS drinking, all mice were necropsied after blood collection, then the colon length was measured, and colon tissue samples were collected. The following experiments were performed: 1) HE staining to observe the histopathological changes in the colon of each group of mice; 2) ELISA to detect the levels of VEGFA in blood and Ang1-7 and Ang Ⅱ in colon tissues; 3) Western blot to detect the expression of ACE2, ACE and PLVAP in colon tissues; 4) Spearman correlation analysis was used to analyze the correlation between ACE2, ACE expression changes and PLVAP expression changes, as well as the correlation between Ang1-7 and Ang Ⅱ content changes and VEGFA content changes. Results: 1) A DSS-induced ulcerative colitis model was successfully established in mice, which showed decreased body weight, highly significant increase in DAI (P < 0.01), highly significant shortening of colon (P < 0.01) and severe pathological changes in colon tissues; 2) Compared with the control group, mice in the DSS group showed colonic hemorrhage, highly significant increase in PLVAP and VEGFA protein expression in colon tissues (P < 0. 01); 3) Compared with the control group, ACE2 and ACE expression in colon tissues of mice in the DSS group were highly significantly upregulated (P < 0.01), and the contents of Ang1-7 and Ang Ⅱ were significantly and significantly increased (P < 0.05 and P < 0.01); 4) Correlation analysis showed that there were positive correlations between ACE2 and ACE expression changes and PLVAP expression changes, as well as Ang1-7 and Ang Ⅱ content changes and VEGFA content changes. The above results suggest that the colonic vascular barrier is damaged during DSS-induced colonic inflammation, the two pathways of RAS in the colon are activated or out of balance, and the activation of ACE/Ang Ⅱ pathways is dominant, suggesting that ACE/Ang Ⅱ is involved in the injury of intestinal-blood barrier in mice with colitis. Activating ACE2 or overexpressing ACE2 to enhance its degradation of Ang Ⅱ to alleviate the damage of intestinal blood barrier may be a new idea or way to treat or alleviate ulcerative colitis.

Key words: renin-angiotensin system, mice, ulcerative colitis, gut-vascular barrier

CLC Number:

S852.21

ZHANG Chonghao, MA Chang, LI Zhiqiang, WU Gang, ZHANG Yuanshu. The Role and Relationship of Renin-angiotensin System in Gut-vascular Barrier Injury in Ulcerative Colitis Mice[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(4): 1756-1765.

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The Role and Relationship of Renin-angiotensin System in Gut-vascular Barrier Injury in Ulcerative Colitis Mice

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