Abstract: SA-PO927
The Mechanism of Intestinal Mucosal Dysfunction Induced by Long-Term Peritoneal Dialysis - Activating the P38MPAK Signaling Pathway
Session Information
- Dialysis: Peritoneal Dialysis - III
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 703 Dialysis: Peritoneal Dialysis
Author
- Jiang, Chen, First teaching hospital of Tianjin university of TCM, Tianjin, China, TIANJIN, China
Background
During long-term PD treatment, the abdominal cavity is always in a high pressure, high glucose environment, resulting in peritoneal and intestinal injury. The peritoneal and intestinal injury lead to a series of complications including endogenous peritonitis, abdominal infection, malnutrition, gastrointestinal disorders inadequate dialysis. Unfortunately, the underlying mechanisms of long-term PD induced intestinal mucosal dysfunction remain unclear The present study was designed to investigate the potential molecular mechanisms of intestinal mucosal dysfunction induced by long-term peritoneal dialysis (PD) treatment.
Methods
Modified peritoneal dialysis rat model and lipopolysaccharide induced IEC-6 cell were used to observe. We examined the intestinal mucosal architecture injury induced by long-term PD by HE staining. Intestinal mucosal permeability was determined by measuring the intestinal clearance of fluorescein-isothiocyanate dextran (FD4), the transepithelial electrical resistance (TER) and the serum levels of D-lactate, Diamine oxidase (DAO) and endotoxin. the potential molecular mechanisms were explored by detecting the mRNA expression of ICAM-1, IL-1β, iNOS and TNF-α via real-time qPCR and the protein expression levels of P-p38MAPK, occludin, ZO-1 and DUSP1 via western blot.
Results
Long-term PD could increase the intestinal mucosal permeability by decreasing the level of TER and increasing the intestinal clearance of FD4, resulting in the serum levels of D-lactate, DAO and endotoxin significantly increased. Co-treatment with Fushen granule could decrease the intestinal mucosal permeability. In vivo and vitro studies, long-term PD markedly decreased the mRNA expression of ICAM-1, IL-1β, iNOS and TNF-α, and further activated the p38MPAK signaling pathway via up-regulating the protein expression of P-p38MPAK and down-regulating the protein expression of occludin, ZO-1 and DUSP1. Co-treatment with Fushen granule could markedly increase the mRNA expression of ICAM-1, IL-1β, iNOS and TNF-α and inhibit the activation of p38MPAK signaling pathway.
Conclusion
The present study is the first to demonstrate that long-term PD induces intestinal mucosal dysfunction by activating the p38MAPK signaling pathway.