| Background and objectivePeritoneal ultrafiltration failure (UFF) is one of the mainly complications during peritoneal dialysis (PD), especially in long-term PD patients, and it has become the chief cause for PD patients to exit the dialysis. Aquaporin (AQP) is a novel family of membrane protein which mediates water transportation acrossing the membranes, and AQP1, AQP3 were reported to be found in peritoneal mesothelial cells and highly correlated with UFF. Nevertheless, enhanced peritoneal neoangiogensis was observed in PD patients through pathologic examination. So we suspected that peritoneal neoangiogensis might attribute to high transportation of small molecules and disappearance of osmotic gradient, and the clinical manifestation was UFF. As we know, neoangiogensis is regulated by many factors such as vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factorβ1(TGFβ1) and so on. bFGF is a peptid factor which is capable of promoting mitosis and neoangiogensis, and it is certain that bFGF play a critical role in tissue fibrosis. In recent years, bFGF mRNA expression was detected by researchers in the peritoneal dialysis effluent, which suggested that mesothelial cells have the potentiality to excrete bFGF and it may be involved in the peritoneal neoangiogensis.High concentration glucose and glucose degradation product (GDP) in no-physiological compatibility peritoneal dialysis liquid were received causes of UFF. In addition, uremic circumstance of chronic renal failure patients in vivo could also lead to UFF. At present, there is few articles about relationship between AQP and UFF under high glucose,uremic circumstance. As for bFGF, there is none.This study is confirmed to detect expressions of AQP1, AQP3 and bFGF in different conditions(high glucose, high osmosis, uremic circumstance), and we want to find the regularity of these indexes expressions and the relationship between AQP1, AQP3 and bFGF, thus we could identify whether there is a common regulative mechanism or not and provide some experimental evidence for the prevention and cure of UFF in clinical.MethodsHuman peritoneal mesothelial cells (HPMCs) were cultured in vitro. When cultured cells grew in good condition and mixed together, we began to give them different stimulus such as high concentration glucose,uremic serum to simulate the PD environment in vivo. Thus cells were divided into several groups: normal control group,high glucose group, uremic group and combined stimulus group. Mannitol group was set up at the same time in order to identify the effect of high osmosis on HPMCs. Cell immunohistochemistry and reverse transcript polymerse chain reaction (RT-PCR) were applied to detect the protein and mRNA expressions of AQP1, AQP3 and bFGF.Results1. AQP1, AQP3 and bFGF protein and mRNA expressions were detected constituently in normal HPMCs;2. High glucose group, mannitol group had a higher AQP1, AQP3 expressions in protein levels when compared to the normal group, while the highest AQP1, AQP3 protein expressions occurred in uremic group and combined stimulus group. The semiquantitative analysis for AQP1, AQP3 mRNA expressions showed that AQP1, AQP3 mRNA expressions were upregulated in high glucose group, uremic group and combined stimulus group in contrast with normal group, and they had significant differences between groups (P<0.05) . But there was no statistically significant of AQP1, AQP3 mRNA expressions between high glucose group and mannitol group (AQP1,P=0.15;AQP3,P=0.45) .3. bFGF protein expression in high glucose group, uremic group and combined stimulus group was higher than normal group, while the mannitol group had a similar level of bFGF protein as normal group. The semiquantitative analysis for bFGF mRNA expression showed that bFGF mRNA expressions were enhanced in high glucose group, uremic group and combined stimulus group in contrast with normal group (P<0.0.001). But there was no statistics difference of bFGF mRNA expression between normal group and mannitol group (P=0.32) .4. AQP1 expression was positive associated with bFGF in high glucose group (r=0.887, P=0.045), uremic group(r=0.910, P=0.032) and combined stimulus group (r=0.899, P=0.038), while there was no correlation between AQP3 and bFGF (P>0.05) .Conclusions1. High glucose and uremic serum could upregulate AQP1, AQP3 expressions, which might affect peritoneal ultrafiltration;2. High glucose enhanced the mRNA expressions of AQP1, AQP3 by elevating osmosis;3. High glucose and uremic serum could upregulate bFGF expression, which might induce the increasement of neoangiogensis. Futher, it might cause the incidence of UFF. |
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