The effect of metformin on intestinal metabolomics in aged septic acute lung injury rats
10.3760/cma.j.issn.1671-0282.2024.09.008
- VernacularTitle:二甲双胍对老年脓毒症急性肺损伤大鼠肠道代谢组学的影响
- Author:
Huoyan LIANG
1
;
Zili XU
;
Simin QIU
;
Kaiyuan ZHANG
;
Zhibo HU
;
Xianfei DING
;
Xiaojuan ZHANG
;
Shaohua LIU
;
Tongwen SUN
Author Information
1. 郑州大学第一附属医院急诊医学部综合ICU，河南省重症医学工程研究中心，河南省重症医学重点实验室，郑州市脓毒症重点实验室，河南省脓毒症诊疗中心，郑州 450052
- Keywords:
Metformin;
Sepsis;
Acute lung injury;
Intestinal metabolites;
Metabolomics;
Aged rats
- From:
Chinese Journal of Emergency Medicine
2024;33(9):1265-1272
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the effect of metformin on intestinal metabolites and its protective effect on lung injury in an elderly sepsis rat.Methods:SD rats were fed at the Animal Laboratory Center of Zhengzhou University, fourteen elderly SD rats were randomly divided into three groups: sham surgery (age-Sham, AgS group, n=4), cecal ligation and perforation induced sepsis (age-Cecal ligation and puncture, AgCLP group, n=5), and oral administration of metformin (100 mg/kg) after 1 h of CLP treatment (age-Metformin, AgMET group, n=5). Collected rat feces 24 h after modeling, and analyzed the composition and inter group differences of metabolites in the feces using liquid chromatography tandem mass spectrometry non targeted metabolomics. Collected rat lung tissues and detected the expression levels of inflammation related genes and pathological changes in the tissue. The visualization of metabolic changes between groups were presented using orthogonal partial least squares discriminant analysis, heatmaps, and unsupervised principal component analysis, respectively. MetaboAnalyst 3.0 was used to evaluate the Pathway analysis of metabolites, and this software was based on the KEGG database and the human metabolome database. Results:The expressions of CCL4 ( F=203.00, P<0.001), CXCL1( F=65.69, P<0.001), IL-6 ( F=38.94, P<0.002), TNF-α ( F=14.85, P=0.005) between two groups of rats were significantly different (all P<0.05). However, there was no significant difference in CCL2 expression between AgCLP group and AgMET group. Furthermore, compared with the AgS group, the relative intensities of 17 metabolites such as 7-methylxanthine, N-Arachidonylglycine and Manolide in AgCLP group were significantly increased, whereas the 9 metabolites such as Phenazone, Gly-Phe and Valyproline were significantly decreased, and metformin treatment could reverse these changes of the above metabolites. Correlation analysis showed that the IL-6 and TNF-α levels were positively correlated with the relative strength of 7-Methylxanthine, N-Arachidonylglycine and other metabolites, but negatively correlated with the Phenazone and Gly-Phe. CCL4 and CXCL1 were positively correlated with Manolide, but negatively correlated with Valyproline. Conclusion:The results of this study showed that metformin improved sepsis induced acute lung injury and regulates the host intestinal metabolites, which might provide a potential and effective treatment for elderly sepsis induced acute lung injury.
