Project title
探究腹膜透析病患腹膜細胞老化現象---腹腔內出血與氧化壓力的影響
Internal ID
NSC97-2314-B002-053-MY3
Principal Investigator
Start Date
August 1, 2008
End Date
July 12, 2009
Organizations
Partner Organizations
Project Web Site
Impact of Hemoperitoneum and Oxidative Stress on Peritoneal Change and Mesothelial Cell Aging in Peritoneal Dialysis Patients = 探究腹膜透析病患腹膜細胞老化現象---腹腔內出血與氧化壓力的影響
Description
Peritoneal fibrosing syndrome (PFS) is a non-rare, but serious complication of peritoneal dialysis (PD). In the past, we had published several research articles of basic and animal studies on PFS. Without exception, these investigations focus mainly on long-term and advanced stage of PFS. As far as we know, researches on early pre-PFS stage is extremely limited. Hemoperitoneum is common in PD patients, with a reported incidence of around 8.4%. Most of the hemoperitoneum occurred in women, during menstruation cycle or asymptomatic. What will happen to human peritoneum and how about the relationship between these repeated episodes of hemoperitoneum and PFS remained undetermined. Our hypothesis is hemoperitoneum may predispose to the development of PFS, through accelerated apoptosis or autophagy of peritoneal mesothelial cells. Meanwhile, this deteriorated cell survival may be accompanied with stimulated local inflammation, cytokines production, and increased matrix production. This project includes cell culture study, animal (rat) model testing and human specimen analysis during a whole period of three years. In the first year, we will try to establish an appropriate rat model of hemoperitoneum. After detected by using PET/CT image program, these experimental rats were sacrificed for pathological study. Cytokines study from body fluid (peritoneal lavage, serum), histopathological specimen of rats and results of image analysis will be re-assembled for data-mining of biomarkers. In the 2nd year, we will test oxidative stress induced by blood, iron and iron-derived molecules on peritoneal mesothelial cells, with the main focus on cellular apoptosis and autophagy. Signal transduction pathways of these cellular changes also will be explored. In the 3rd year, we will test whether antioxidant (N-acetylcysteine), or iron-chelating agent (deferroxamine) can suppress cellular change or the accompanied matrix production. During this 3-year period, we scheduled to enroll over thirty patients on long-term PD to study human biomarkers in drained PD fluid, and correlate them with individual PET test characteristics. Through this 3-year, from in-vitro and in-vivo experiments to clinical survey, we will make it clear whether hemoperitoneum really benign. Or in contrast, we may prove this subclinical hemoperitoneum event may do harm to human peritoneum and contribute to some magnitude to the development of PPFS. If the latter is true, we also may have tested potential protective roles of antioxidant or iron-chelating agent used during hemoperitoneum. Our work is novel and has high clinical relevance in patient care of PD therapy.