Low Molecular Weight Heparin (LMWH) Improves Peritoneal Function and Inhibits Peritoneal Fibrosis Possibly through Suppression of HIF-1α, VEGF and TGF-β1

BACKGROUND: Peritoneal fibrosis is the major cause of ultrafiltration failure, and intraperitoneal administration of Low Molecular Weight Heparin (LMWH) was reported to protect peritoneal function. But the exact mechanism of its influence on peritoneal structure and function is still unknown. METHODS: A fibrosis model of rat was established by intraperitoneal (IP) administration of PD fluid and Erythromycin Lactobionate. Fifty-two rats were randomly divided into 6 groups: (1) normal control group (CON, n = 6); (2) normal saline group (NS, n = 10); (3) high-glucose group (GLU, n = 10); (4) heparin group (HEP, n = 6); (5) low dose LMWH group (LLMWH, n = 10); (6) high dose LMWH group (HLMWH, n = 10). Two hour peritoneal equilibration test was performed after 28 days of intervention. The peritoneum, mesentery and omentum were harvested, and evaluated by Hematoxylin-Eosin and Masson Trichrome staining. The expressions of HIF-1α, VEGF and TGF-β1 in parietal peritoneum were detected by IHC and RT-PCR (Reverse Transcriptase Polymerase Chain Reaction). RESULTS: Compared with group CON and NS, ultrafiltration volume and D2/D0 glucose in group GLU decreased significantly, D/Purea (Dialysate-Plasma ratio of urea), D/Palb (Dialysate-Plasma ratio of albumin), peritoneal thickness, neoangiogenesis and inflammatory reaction increased significantly (all P<0.05). Administration of heparin and LMWH markedly alleviated these above pathological changes. The protein and mRNA levels of HIF-1α, VEGF and TGF-β1 increased significantly in group GLU, and decreased significantly after administration of LMWH in a dose-dependent manner. CONCLUSIONS: LMWH ameliorates peritoneal function and inhibits peritoneal fibrosis, possibly through suppression of HIF-1α, VEGF and TGF-β1.