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-α and IL-6 at 24 h after CLP. The correlational analysis between plasma of IL-6/TNF-α and metabolites suggested that acetylcholine, spermine, phenylalanine, threonine of plasma and phosphatidylcholine (36:4) of lung tissues were significantly associated with IL-6/TNF-α 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.
Highlights
Sepsis has been defined as a life-threatening organ dysfunction attributed to the host's dysregulated response to infection (Singer et al, 2016)
The mortality rate in the cecal ligation and puncture (CLP) group was higher than SC group (P = 0.003) and CLP-Adipose-derived mesenchymal stem cells (ADMSCs) group (P = 0.501)
We detected plasma concentration of TNF‐a and IL-6 at 24 h after CLP and found levels of inflammatory factors upregulated in the CLP group and significantly down-regulated in the CLP-ADMSCs group (Figure 1B)
Summary
Sepsis has been defined as a life-threatening organ dysfunction attributed to the host's dysregulated response to infection (Singer et al, 2016). Many pro-inflammatory cytokines, such as TNF-a and IL-6, reportedly triggered in sepsis, which caused an overwhelming immune response against the infection (Cecconi et al, 2018; Nowill et al, 2019). Adipose-derived mesenchymal stem cells (ADMSCs) treatment has shown a lot of beneficial effects on sepsis. Some studies reported mesenchymal stem cells (MSCs) could alleviate immune response and reduce mortality by down-regulating pro-inflammatory and up-regulating anti-inflammatory cytokines in sepsis (Condor et al, 2016; Ou et al, 2016). Our previous research has suggested that ADMSCs secrete a large amount of sTNFR1 to block the activity of TNF-a, thereby reducing the expression of NF-kB, AP-1, and P38 MAPK in sepsis induced ALI (Ding et al, 2019). The mechanism of ADMSCs treatment still needs lot of experiments to explore
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