Background: In sepsis, vitamin D binding protein (VDBP) has been shown to be low-expressed. The current study examined the relationship between serum VDBP level and liver injury in sepsis patients, as well as in a mouse model for sepsis and in cultured liver epithelial cell line exposed to lipopolysaccharide (LPS). Methods: The human study included 78 sepsis patients and 50 healthy volunteers. Sepsis patients were categorized into sepsis survivor group (n=43) and sepsis non-survivor group (n=35) based on 28-day mortality for data analysis. Adult male C57BL/6 mice were subjected to cecal ligation and puncture (CLP). Serum samples were collected on days 1, 3, 5 and 7 to determine the levels of VDBP, 25-hydroxyvitamin D [25(OH)D3], 1,25-dihydroxyvitamin D [1,25(OH)2D3], interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Potential protective effects of VDBP overexpression against LPS-induced liver damage were examined in cultured THLE2 cells. Results: Serum levels of VDBP, 25(OH)D3, and 1,25(OH)2D3 were significantly lower in sepsis patients vs. the healthy control (P<0.001), as well as in the sepsis non-survivor group vs. the sepsis survivor group (P<0.001, P=0.0338, or P=0.0013, respectively). Lower serum VDBP level was associated with higher Acute Physiology and Chronic Health Evaluation (APACHE)Ⅱ score (r=–0.2565, P=0.0234) and Sequential Organ Failure Assessment (SOFA) score (r=–0.3522, P=0.0016), but lower serum albumin (ALB, r=0.4628, P<0.001) and total protein (TP, r=0.263, P=0.02). In CLP mice, there was a 5-day period of serum VDBP reduction, followed by return towards the baseline on day 7. VDBP was also decreased in LPS-treated THLE2 cells (P<0.001). VDBP overexpression reduced LPS-induced THLE2 damage. Reduced damage was associated with decreased oxidative stress and inactivation of the c-Jun N-terminal kinase signaling pathway. Conclusions: VDBP may be protective against sepsis-induced liver injury.

Kun Xiao;Du?Chao Zhang;Ye Hu;Li?Cheng Song;Jian?Qiao Xu;Wan?Xue He;Pan Pan;Yu?Wei Wang;Li?Xin Xie

Center of Pulmonary and Critical Care Medicine,Chinese People's Liberation Army(PLA)General Hospital,No.28,Fuxing Street,Haidian District,Beijing 100853,China;Department of Pulmonary and Critical Care Medicine,Beijing Shijitan Hospital,Beijing 100071,China;Medical School of Chinese People's Liberation Army(PLA),Chinese PLA General Hospital,Beijing 100853,China;Department of Geriatric Comprehensive Surgery,the Second Medical Center and National Clinical Research Center for Geriatric Diseases,Chinese PLA General Hospital,No.28,Fuxing Street,Haidian District,Beijing 100853,China

军事医学研究（英文）

[1]Kun Xiao;Du?Chao Zhang;Ye Hu;Li?Cheng Song;Jian?Qiao Xu;Wan?Xue He;Pan Pan;Yu?Wei Wang;Li?Xin Xie-.Potential roles of vitamin D binding protein in attenuating liver injury in sepsis)[J].军事医学研究（英文）,2022(05):543-552

THLE2

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