Abstract
The preservation of the endothelial glycocalyx (eGC) showed benefits for the treatment of sepsis. The sedative medicine dexmedetomidine (DEX) has been studied to be able to preserve the eGC that has not been shown in sepsis. As recently developed experimental techniques, microfluidics-based in vitro models showed merits in the physiological and pathological study of vascular endothelium and can be applied for the establishment of sepsis-related glycocalyx degradation. This study is based on a PDMS-based microfluidic system to assess the protective role of the DEX treatment in preserving the eGC in sepsis. The PDMS-based microfluidic system was applied to the culture of human umbilical vein endothelial cells (HUVECs). The microfluidic-based endothelial culture was validated and then assessed for the effects of DEX treatment (100 and 500 nM) on the eGC degradation caused by sepsis. The 500 nM DEX treatment had a significantly higher expression of glycocalyx with the fluorescent intensity relative to the control at 1.07, as compared to the LPS treatment (0.82, P < 0.001) and the 100 nM DEX treatment groups (0.93, P < 0.05). The ELISA assay showed that the 500 nM DEX treatment could significantly (P < 0.05) inhibit the concentration of hyaluronan (HA, the biomarker of glycocalyx degradation) (21.48 ng/mL) in the microfluidic fluids as compared to that of LPS group (24.65 ng/mL). Moreover, this group was also effective (P < 0.01) to inhibit the LPS-induced low expression of Ve-cadherin (0.91) with the intensity relative to control at 1. The DEX treatment at 500 nM was proved to be effective for preserving sepsis-related glycocalyx degradation.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
This study was financially supported by the Fundamental Research Funds for the Central Universities (No. JKF-YG-20-B008 & No. YWF-19-BJ-J-132) and the National Natural Science Foundation of China (No. 11674019 & No. 12072010). Besides, this work was also partially funded by the National Natural Science Foundation of China under Grant No. 82172401.
Funding
This work was supported by the National Natural Science Foundation of China, under Grant No. 82172401, No. 12072010 and No. 11674019, and Fundamental Research Funds for the Central Universities, under Grant No. JKF-YG-20-B008 and No. YWF-19-BJ-J-132.
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All authors contributed to the study conception and design. WL performed the majority of experiments, data collection and analysis, and wrote the manuscript. LY prepared the primary HUVECs, LPS solution, and DEX medicine, and performed the partial experiments and data collections. WH and SY made the contribution to the fabrication of the PDMS-based microfluidic system and the performance of preliminary experiments. YX, PZ, and TW made the contribution to the revision of data analysis and manuscript.
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Liao, W., Yi, L., He, W. et al. A PDMS-based microfluidic system for assessment of the protective role of dexmedetomidine against sepsis-related glycocalyx degradation. Microfluid Nanofluid 27, 29 (2023). https://doi.org/10.1007/s10404-023-02635-6
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DOI: https://doi.org/10.1007/s10404-023-02635-6