Studies On The Influence Of Epithelial-Dendritic Cell Transformation On Hemorrhagic Shock Related Systemic Inflammatory Response Syndrome And The Protective Effect Of Vitamin C

Objectives: To investigated the roles of epithelial-dendritic cell transformation(EDT) characterized by the expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin(DC-SIGN) in the occurrence of systemic inflammatory response syndrome(SIRS) induced by hemorrhagic shock(HS), the protective effect of Vitamin C(Vit C), and the potential mechanisms.Methods: We cultured the rat intestinal epithelial cells(IEC-6) in anoxic condition, some of which were protreated with Vit C(20-100 u M). After hypoxic culture for 2, 6, 24, and 48 hours, the expression levels of DC-SIGN, E-cadherin and Glycogen synthase kinase-3β(GSK-3β) in IEC-6 cells, the IL-1β and IL-6 concentrations in cell culture medium were measured(n=3/group).To investigate the potential mechanism, we inhibited E-cadherin expression by si RNA, and inhibited GSK-3β activity by TDZD-8 respectively. Then we observed the DC-SIGN and E-cadherin expression levels in IEC-6 under anoxic condition with or without Vit C(n=3/group).The in vivo study was conducted by establishing SD rat HH model by withdrawing blood from the rat femoral artery. The HS rats were pretreated with Vit C(100mg/kg) or normal saline(NS) before resuscition. We observed the expression levels and location of DC-SIGN in the intestines and kidneys, the histological damage, the pro-inflammatory cytokine levels as well as serum level of biochemical indicators 2, 6, and 24 hours after HS, with or without Vit C pretreatment(n=6/group).Results: When we cultured the rat intestinal epithelial IEC-6 cell in anoxic condition more than 2 hours, the expression level of DC-SIGN was upregulated markedly. The E-cadherin expression level and the activity of GSK-3 β was depressed simultaneously(p<0.05). Vit C inhibited the upregulation of DC-SIGN induced by hypoxia in a concentration-depented manner. The dicreasing trends of E-cadherin and GSK-3βactivity induced by hypoxia were also inhibited(p<0.05). When the E-cadherin experession was interfered by si RNA in advance,the inhibitive effect of Vit C on DC-SIGN expression was diminished(p<0.05). When the GSK-3βactivity was inhibited in advance by the specific inhibitor TDZD-8, the protective effect of Vit C on the expression of E-cadherin under anoxic condition was also abolished(p<0.05)。Hemorrhagic shock induced DC-SIGN expression in rat intestines and kidneys. Vit C(100mg/kg)inhibited DC-SIGN expression markedly(p <0.05). Vit C pretreatment relieved the histological damages, the the pro-inflammatory cytokines levels as well as serum level of biochemical indicators in the early stage of HS(p <0.05)Conclusion: Hemorrhagic shock or hypoxic culture may induce epithelial-dendritic cell transformation; Vit C significantly alleviated the hemorrhagic shock induced multi-organ inflammation by suppressing epithelial-dendritic cell transformation.