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Lipopolysaccharide induced intestinal epithelial injury:a novel organoids-based model for sepsis in vitro

查看全文 作　　者：Sisi [1]Huang;Sheng [1]Zhang;Limin [1]Chen;Xiaojun [1]Pan;Zhenliang [1]Wen;Yizhu [1]Chen;Lidi [1]Zhang;Jiao [2]Liu;Dechang [1]Chen 高影响力作者 机构地区：[1]Department of Critical Care Medicine,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200020,China;[2]Department of Critical Care Medicine,Ruijin Hospital North,Shanghai Jiao Tong University School of Medicine,Shanghai 201801,China高影响力机构 出　　处：《Chinese Medical Journal》索引2022年第135卷第18期,共8页高影响力期刊 基　　金：supported by grants from the National Natural Science Foundation of China(Nos.81873944 and 81971869);the Shanghai Science and Technology Commission(No.20DZ2200500). 摘　　要：Background: Advances in organoid culture technology have provided a greater understanding of disease pathogenesis, which has been rarely studied in sepsis before. We aim to establish a suitable organoids-based intestinal injury model for sepsis.Methods: Stable passaged organoids were constructed and pre-treated with lipopolysaccharide (LPS) to mimic sepsis-induced intestinal injury. The LPS-induced sepsis model was used as a reference. We used quantitative real-time polymerase chain reaction to evaluate the RNA levels of inflammatory factors and antimicrobial peptides. Enzyme-linked immunosorbent assay was used to evaluate the protein levels, hematoxylin and eosin staining was used to evaluate the pathology of the small intestine of mice, and immunohistochemistry and immunofluorescence were used to evaluate the intestinal epithelial barrier function. Perkin Elmer OperettaTM was used to obtain high-resolution images of three-dimensional organoids.Results: An LPS concentration >150 μg/mL after 24 h was identified to cause organoid growth restriction. The fluorescence intensity of zonula occludens-1 and occludins at LPS concentrations >100 μg/mL decreased significantly after 24 h. After LPS stimulation for 8 h, the RNA expression levels of interleukin (IL)-1α, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, IL-6, and regenerating islet-derived protein 3 alpha, beta, and gamma increased. These results resembled those of intestinal epithelial layer alterations in a mouse sepsis model. For IL-10, the RNA expression level increased only when the LPS level >200 μg/mL for 24 h.Conclusions: This study provides the primary intestinalin vitro model to study the effects of LPS-induced intestinal injury resembling sepsis. This model provides a platform for immune associated mechanism exploration and effective drug screening. 关 键 词：ORGANOIDS SEPSIS LIPOPOLYSACCHARIDE Barrier function Inflammatory factors
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