| OBJECTIVE: Peritoneal dialysis is an important substitutive therapy for patients with end stage renal disease. Peritoneal fibrosis, which can result in the loss of peritoneal structure and function, is one of the most serious causes of failure in long-term peritoneal dialysis. Recently, all-trans retinoic acid (ATRA) has been used as an antifibrosis drug in many experimental models. It was hypothesized that ATRA would be effective on peritoneal fibrosis. This study is to observe the impact of ATRA on peritoneal fibrosis induced by high glucose peritoneal dialysate in rats, and investigate its mechanism initially.METHODS: Thirty-two male Sprague-dawley(SD) rats were randomly divided into four groups(n=8): control group received normal saline (0.9%,10ml/d) plus identical voluminal solvent dimethyl sulphoxide(DMSO) diluted by phosphate buffer saline(PBS); model group received peritoneal dialysate (4.25%, 10ml/d) plus identical voluminal solvent; small dose ATRA group(A1) and large dose ATRA group(A2) received peritoneal dialysate (10ml/d) plus ATRA 2mg/kg·d and 5mg/kg·d. All injections were performed once daily intraperitoneal injection(IP) for 4 weeeks. All the rats eat and drink freely and the environment for them keep airing, homeothermia and quiet. After 4 weeks,1 hour peritoneal equilibration test(PET) was performed with 4.25% peritoneal dialysate. Dialysate-to-plasma urea ratio (D/Purea), glucose reabsorption (D1/D0), ultrafiltration volume(UF) were examined. After that, all the rats were sacrificed. TGF-131,CTGF,α-SMA and COL-Iprotein expression were measured by immunohistochemistry. TGF-β1mRNA expression were examined with real time polymerase chain reaction (RT-PCR).RESULTS:①Compared with the control,A1, A2 group,UF and D1/D0 had decreased significantly (P＜0.05) in the model group, and D/Purea increased significantly (P＜0.05). Furthermore, UF and D1/D0 of A2 group were also significantly higher than that of A1 group (P＜0.05). There was no statistical difference between A2 group and the control group (P＞0.05).②In the control group,the peritoneum was thin and slick.While in the model group,it was thicker and some mesothelial cells detached from it. In A1 and A2 group, pathological changes was significantly lessened as compared to the model group.③In the control group, expression of TGF-β1,CTGF,α-SMA and COL-Ⅰprotein in peritoneum was weak.But the level of them in the model group was significantly higher than any other groups (P＜0.05). Compared with A1 group, the accumulation of these protein in peritoneum was significantly decreased in A2 group (P＜0.05).④In the control group, TGF-β1mRNA in peritoneal mesothelial cells was weak. The expression of TGF-β1mRNA in the model group was higher than any other groups (P＜ 0.05). After intervention with ATRA ,the level was significantly decreased (P＜0.05). And there was also statistical difference between A1 and A2 group (P＜0.05). The expression of that in A2 group was lower as compared to that of A1 group.CONCLUSION:①High glucose peritoneal dialysate could induce peritoneal fibrosis.②ATRA had preventive and therapeutic effect on peritoneal fibrosis induced by high glucose peritoneal dialysate. And the effect also had dose dependence.③ATRA alleviated peritoneal fibrosis may through down-regulation of TGF-β1,CTGF,α-SMA and COL-Ⅰ.
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