| Peritoneal dialysis(PD) is an important dialysis modality, but many limitations exist. Ultrafiltration failure is the main etiology of treatment discontinuation for long-term PD patients. How to protect the peritoneum from peritoneal fibrosis then to prolong the course of peritoneal dialysis is the focus for many researchers. Now it is wildly believed that epithelial-mesenchymal transition(EMT) is the pathological basis of the peritoneal fibrosis, the direct contributor to ultrafiltration failure. However, aquaporin-1(AQP1) dysfunction may be another reason for ultrafiltration failure, given that AQP1 mediates almost 50% of the ultrafiltration capacity. AQP1 is a special water channel located on the membranes of multiple cell types, including capillary endothelia, erythrocytes, renal tubular epithelia, and peritoneal mesothelial cells. There are few reports concerning the relationship between AQP1 and fibrosis. The purpose of this paper is to observe the effection of AQP1 on the course of peritoneal dialysis caused by peritoneal dialysis.In this study, we first used a special silicone catheter(mouse port; Access Technologies, Strategic Applications, Libertyville, IL, USA) through a subcutaneous tunnel to the back. The other end of the catheter was implanted from one side of the peritoneal wall into the peritoneal cavity. Then we injected the 4.25% glucose peritoneal dialysate(Baxter Guangzhou, China) through the chamber for 28 days. Mice were sacrificed at day 28, and following sacrifice, we harvested the other side upper portion of the abdominal wall. We detect the formation of peritoneal fibrosis by Masson and immunofluorescence methods, then the model of peritoneal fibrosis caused by peritoneal dialysis was established. At the same time, we measured the expression of AQP1, which expressed in PMC showed higher in control group, while expressed in fibrosis peritoneum showed located on capillary endothelial cells.Then we divided genetic knockout of AQP1 in a CD1 background mice into four groups: a control group, a dialysis group, an AQP1 knockout group, and an AQP1 knockout dialysis group. The two dialysis groups received 4.25% glucose dialysate intraperitoneally for 28 days, and then took the abdominal wall for the research of relationship between AQP1 and peritoneal fibrosis. We found that mice in both dialysis groups showed fibrotic changes, which were most severe in the AQP1 knockout dialysis group; the peritoneal thickness in the AQP1 knockout dialysis group was also thicker than that in the dialysis group(P<0.05). We used the electron microscopy to detect ultrastructural of PM, and observed changes in microvilli and vacuolar degeneration in mesothelial cells from all groups except the control group. The basement membrane was damaged in the group of AQP1 knockout dialysis group, and peritoneal mesothelial cells were disrupted and detached in this group. At the same time, we detected the blood glucose in each groups, and there were no obvious difference between each group.Continue we established type 1 diabetes mouse model used genetic knockout of AQP1 in a CD1 background mice which were induced with streptozotocin(STZ). At the forth month, we sacrificed the mice and observed the peritoneum change in the case of endogenous hyperglycemia. The results showed that, there were no obvious fibrosis, no obvious change on peritoneum thickness in each group. But the peritoneal mesothelial cells and nuclears had a shape change, from flat spindle to a short cylindricity.In conclusion, we haved succeed in implanting a catheter into a mouse abdomen to make a mouse model of peritoneal fibrosis caused by chronic peritoneal dialysis. This is very helpful in study the mechanism of fibrosis and choose a different dialysate, and improve the treatment of peritoneal dialysis and et,al. Second, AQP1 plays an important role in maintaining the normal function of peritoneal mesothelial cells. AQP1 can protect the peritoneum from fibrosis or even delay this pathological change during long-term peritoneal dialysis(PD) with hypertonic solution retention. Thus, it may be a factor to prolong the peritoneal dialysis and decrease the fibrosis. At last, we used the type 1 diabetic mouse model to observe the change of peritoneum in the case of high blood glucose. We found no change on peritoneum thickness but cells shape, which suggested cells damage, while AQP1 can protect cells from this damage. Thus, to increase the expression of AQP1 may be a new therapy strategies to protect the peritoneum from fibrosis or even delay this pathological change during long-term PD. |
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