| Background and ObjectivePeritoneal dialysis(PD) is a preferred alternertive treatment for end-stage renal disease because of its advantages such as better protection for residual renal function, lower rate of cardiovascular events,convience of operation,lower costs,etc...However, the incidence of ultrafiltration failure(UUF) increases gradually as the duration of PD prolongs.Recent datas indicate that as many as 36% patients with more than 6y history of PD develop UFF,which results in withdrawing from PD.Researchers paid their attention to angiogenesis and fibrosis of peritoneam which were considered to play important role in the pathogenesis fo UFF.Hypoxia inducible factor-la(HIF-lα)..is an important regulator of oxygen hemostasis in both cells and tissues. HIF-la was expressed in renal trauma, aristolochic acid nephropathy, renal cell cancer, tumor and other diseases. It regulates the transcription of several target genes including connective tissue growth factor(CTGF) which participates in the process of angiogenesis and fibrosis of tissues.Recent study demonstrates that ischemia and hypoxia exist in the process of fibrosis of Renal interstitial in CKD patients. The abnormal expression of HIF-1αin kidney tissues induce the overexpression of CTGF in the epithelial cells of renal tubules.However,it is not known whether the expression of HIF-1α. and CTGF exists in peritoneum and whether the the expression of HIF-lα. and CTGF leads to peritoneal fibrosis.As a result,we established 5/6 nephrectomy uremic and peritoneal dialysis rats model to mimic the peritoneal dialysis procedure of human. We selected HIF-1α, CTGF and. a-smooth muscle actin(a-SMA) as the detection index and expolre their role in UUF and hence to provide new idea in prevention and treatment of UUF.MethodsThirty-two male SD rats of clean grade whose weighing was 180-200g were used in this study and were randomly divided into four groups:normal control rats(group A,n=8), affected operated rats(group B,n=8), renal failure without PD rats(group C,n=8) and rats dialyzed with 4.25% peritoneal solution (group D,n=8). We established the uremia rats model by 5/6 nephrectomy. From these uremia rats, the peritoneal dialysis (PD) rats model was randomly established. Regular peritoneal dialysis were given with 4.25% PD solutions in the rats from D groups per day.After regular PD for 28 days, with immunohistochemical and RT-PCR,the mRNA and protein expressions of HIF-la and CTGF were defected in rats'peritoneal tissues of each group. The alpha-smooth muscle actin(a-SMA) concentration were defected, to investigate the degree of peritoneal fibrosis. Statistical analysis was performed to compare with their expressions and co relationship in each group.Significance was defined as a=0.05.Results1. The mRNA and protein of HIF-1α. and CTGF were expressed in each group.The expression of HIF-1αand CTGF was mildly elelvated in Group B compared with Group A but without statistical significance(P>0.05). However,the expression of HIF-1αand CTGF was elelvated significantly in Group C and Group D compared with Group A and Group B(P<0.05).2. The expression of a-SMA was detected in Group C and Group D but not Group A and Group B.And the expression ofα-SMA was up-regulated in Group D compared with Group C(P<0.05).3. There was a positive correlation between HIF-1αand CTGF in protein level(r=0.763).ConclusionsPeritoneal fibrosis in PD rats may be related to HIF-1α, CTGF protein and mRNA upregulation. |
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