Astragalaside IV Inhibits Colonic Adenomatous Polyps Formation in High-fat Diet-fed Apc Min/+ Mice by Regulating Serum Metabolomics
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2022.0607
- VernacularTitle:基于血清代谢组学研究黄芪甲苷抑制高脂喂养的Apc Min/+小鼠结肠腺瘤性息肉形成
- Author:
Qiu-lan HE
1
;
Lu-ping WEN
2
;
Gui-ming LI
3
;
Zhong-yuan LIN
1
;
Feng-jiao GAO
1
;
Wen-qi HUANG
1
Author Information
1. Department of Anesthesiology， The First Affiliated Hospital of Sun Yat-sen University， Guangzhou 510080， China
2. Anorectal Section， Affiliated Hospital of Xuzhou Medical University， Xuzhou， 221000，China
3. Department of Colorectal and Anal Surgery， The Sixth Affiliated Hospital of Sun Yat-sen University， Guangzhou， 510655，China
- Publication Type:Journal Article
- Keywords:
adenomastous polyps;
Astragaloside IV;
colon;
metabolomics;
N-Acetyl-α-D-Glucosamine
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2022;43(6):916-927
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the preventive effects of Astragaloside IV （ASIV） on the formation of colonic adenomatous polyps （CAP） in high-fat-fed （HF） mice with adenomatous polyposis mutation （Apc Min/+） and its regulation mechanism on serum metabolite disorders. MethodsA total of 24 mice were evenly assigned to Apc Min/+ mice group （Con， n=8）， high-fat diet-fed Apc Min/+ mice group （HF， n=8）， and ASIV treatment group （HF-ASIV， n=8）. Apc Min/+ mice in HF group and HF-ASIV group were given high-fat diet for 8 consecutive weeks to construct CAP mouse model. Meanwhile， Apc Min/+ mice in HF-ASIV group were given 50 mg/kg ASIV every other day for 8 weeks. Daily amount of water intake， food intake and body weight of mice in each group were recorded. At the end of the 8th week， mice were sacrificed for serum and the distal and proximal colon. The number of colonic polyps in each group was recorded. Hematoxylin-eosin （H&E） staining was used to observe the morphological changes of the proximal colon. Immunohistochemistry （IHC） was applied to analyze the amount of COX2 positive cells in the proximal colon. The expression levels of IL-1 β and TNFα in intestinal wall were detected by QRT PCR. Non-targeted metabolic profiling of mouse gut by liquid-phase mass spectrometry was used to screen for differential metabolites and perform functional enrichment. ResultsNo mice died in each group during experiment.ASIV effectively reduced the size and the number of the CAPs that accompanied with the downregulation of inflammatory signaling molecules （COX-2， IL-1 β and TNFα）. Alcian blue and lysozyme staining showed ASIV improved the gut epithelium by promoting goblet and Paneth cells population. Significant differences in metabolite OPLS-DA scores between groups were noted （P < 0.001； P = 0.02）. Compared with HF group， 13 differential metabolites in the serum of HF-ASIV group were significantly recalled， and the levels of the metabolites functionally enriched to N-acetyl-α-D-glucosaminyl-diphosphate were significantly increased in the positive and negative ion modes （P < 0.05） ， which was negatively correlated with the number of medium-sized adenomas （P < 0.01）. ConclusionASIV reduced the number of colonic adenomatous polyps in high-fat-fed Apc Min/+ mice and was closely associated with reduced intestinal wall inflammation and regulation of serum metabolite N-acetyl-α-D-glucosamine-diphosphate levels.
