Protective Effect of Ulinastatin on Hydrogen Peroxide-induced Intestinal Epithelial Barrier Disruption
10.3969/j.issn.1008-7125.2017.04.007
- VernacularTitle:乌司他丁对过氧化氢诱导的肠上皮屏障损伤的保护作用
- Author:
Gai WANG
;
Zhihua WANG
;
Hongnian DUAN
;
Huan XU
;
Jiangtao MA
;
Xinhui LIU
;
Jiaqi LIU
;
Ning LI
;
Chunpeng CHANG
;
Jingxia HAO
- Keywords:
Ulinastatin;
Hydrogen Peroxide;
Intestinal Mucosal Barrier;
Epithelial Cells;
Tight Junctions
- From:
Chinese Journal of Gastroenterology
2017;22(4):224-228
- CountryChina
- Language:Chinese
-
Abstract:
Background: Disruption of tight junctions between intestinal epithelial cells followed by loss of barrier function is crucial for the pathogenesis and progression of a variety of gastrointestinal disorders.Aims: To investigate the protective effect of ulinastatin on hydrogen peroxide (H2O2)-induced intestinal epithelial barrier disruption.Methods: Model of intestinal epithelial monolayer barrier was established with Caco-2 cells in vitro,and then divided into four groups: blank control group (without any intervention),H2O2 group (500 μmol/L H2O2),low-dose (500 U/mL) and high-dose (3 000 U/mL) ulinastatin groups (ulinastatin + H2O2).Level of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were detected;transepithelial electrical resistance (TEER) and flux of sodium fluorescein were measured to assess the barrier function;expression and localization of two tight junction proteins,ZO-1 and occludin were evaluated by Western blotting and immunofluorescence;ultrastructure of tight junctions was observed by transmission electron microscopy (TEM).Results: Compared with the blank control group,treatment of Caco-2 cell monolayers with H2O2 resulted in increase in level of MDA,flux of sodium fluorescein and decrease in activity of SOD,TEER and expressions of ZO-1 and occludin (P all ＜0.05).TEM and immunofluorescence showed that the brusher border of Caco-2 cells in H2O2 group was destroyed,the cell-cell junction was vague and the localization of ZO-1 and occludin was discontinuous and the fluorescence intensity was extremely low.While in ulinastatin groups,especially the high-dose group,all the indices above-mentioned were significantly improved (P all ＜0.05).Conclusions: Ulinastatin protects intestinal epithelial monolayer barrier against H2O2-induced disruption at least partially by its antioxidant activity and modulating expression and localization of tight junction proteins.
