Dataset Information

Metabolomic Analysis of the Effects of Adipose-Derived Mesenchymal Stem Cell Treatment on Rats With Sepsis-Induced Acute Lung Injury.

ABSTRACT: Given the high mortality associated with sepsis, there is an urgent need for a full understanding of sepsis pathophysiology and finding new therapeutic regimens. Adipose-derived mesenchymal stem cells (ADMSCs) has been proven to have anti-inflammatory effects and could be used to treat cecal ligation and puncture (CLP) induced lung and liver injury in septic rat models. In this study, we used metabolomics to investigate small molecule metabolites between CLP and ADMSCs treatment groups. Sixty SD rats were randomly assigned to the sham operation group (SC group), the CLP group, and the CLP+ADMSCs group (CLP-ADMSCs group). We used liquid mass spectrometry-chromatography to detect metabolic changes in plasma and lung tissues. Compared with the SC group, the metabolic profile of plasma and lung tissues changed significantly 24 h after CLP. Moreover, 22 and 11 main differential metabolites involved in amino acid and glycerophospholipid metabolism were found in plasma and lung tissues, respectively. After the rats were injected with ADMSCs, these differential metabolites were reverse-regulated both in plasma and lung tissues. Besides, ADMSCs improved the survival rate and down-regulated the concentration of TNF-? and IL-6 at 24 h after CLP. The correlational analysis between plasma of IL-6/TNF-? and metabolites suggested that acetylcholine, spermine, phenylalanine, threonine of plasma and phosphatidylcholine (36:4) of lung tissues were significantly associated with IL-6/TNF-? in CLP and CLP-ADMSCs groups. ADMSCs might reverse abnormal metabolic pathways by reducing anti-inflammatory factors in sepsis-induced ALI. Our findings may provide novel metabolic mechanism of ADMSCs therapy for sepsis.

SUBMITTER: Cui Y

PROVIDER: S-EPMC7311761 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Metabolomic Analysis of the Effects of Adipose-Derived Mesenchymal Stem Cell Treatment on Rats With Sepsis-Induced Acute Lung Injury.

Cui Yuqing Y Liu Shaohua S Zhang Xiaojuan X Ding Xianfei X Duan Xiaoguang X Zhu Zijia Z Zhang Ji J Liang Huoyan H Wang Dong D Zhang Guojun G Yu Zujiang Z Yang Jianjun J Sun Tongwen T

Frontiers in pharmacology 20200617

Given the high mortality associated with sepsis, there is an urgent need for a full understanding of sepsis pathophysiology and finding new therapeutic regimens. Adipose-derived mesenchymal stem cells (ADMSCs) has been proven to have anti-inflammatory effects and could be used to treat cecal ligation and puncture (CLP) induced lung and liver injury in septic rat models. In this study, we used metabolomics to investigate small molecule metabolites between CLP and ADMSCs treatment groups. Sixty SD ...[more]

PMID: 32625095

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Project description:BACKGROUND:We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) may ameliorate sepsis-induced acute lung injury (ALI) and change microorganism populations in the gut microbiota, such as that of Firmicutes and Bacteroidetes. METHODS:A total of 60 male adult Sprague-Dawley (SD) rats were separated into three groups: the sham control (SC) group, the sepsis induced by cecal ligation and puncture (CLP) group, and the ADMSC treatment (CLP-ADMSCs) group, in which rats underwent the CLP procedure and then received 1?×?106 ADMSCs. Rats were sacrificed 24?h after the SC or CLP procedures. To study the role of ADMSCs during ALI caused by sepsis and examine the impact of ADMSCs on the gut microbiome composition, rat lungs were histologically evaluated using hematoxylin and eosin (H&E) staining, serum levels of pro-inflammatory factors were detected using enzyme-linked immunosorbent assay (ELISA), and fecal samples were collected and analyzed using 16S rDNA sequencing. RESULTS:The serum levels of inflammatory cytokines, tumor necrosis factor (TNF)-? and interleukin (IL)-6, were significantly increased in rats after the CLP procedure, but were significantly decreased in rats treated with ADMSCs. Histological evaluation of the rat lungs yielded results consistent with the changes in IL-6 levels among all groups. Treatment with ADMSCs significantly increased the diversity of the gut microbiota in rats with sepsis. The principal coordinates analysis (PCoA) results showed that there was a significant difference between the gut microbiota of the CLP-ADMSCs group and that of the CLP group. In rats with sepsis, the proportion of Escherichia-Shigella (P?=?0.01) related to lipopolysaccharide production increased, and the proportion of Akkermansia (P?=?0.02) related to the regulation of intestinal mucosal thickness and the maintenance of intestinal barrier function decreased. These changes in the gut microbiota break the energy balance, aggravate inflammatory reactions, reduce intestinal barrier functions, and promote the translocation of intestinal bacteria. Intervention with ADMSCs increased the proportion of beneficial bacteria, reduced the proportion of harmful bacteria, and normalized the gut microbiota. CONCLUSIONS:Therapeutically administered ADMSCs ameliorate CLP-induced ALI and improves gut microbiota, which provides a potential therapeutic mechanism for ADMSCs in the treatment of sepsis.

Dataset Information

Metabolomic Analysis of the Effects of Adipose-Derived Mesenchymal Stem Cell Treatment on Rats With Sepsis-Induced Acute Lung Injury.

Publications

Metabolomic Analysis of the Effects of Adipose-Derived Mesenchymal Stem Cell Treatment on Rats With Sepsis-Induced Acute Lung Injury.

Similar Datasets

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