Tianjin Medical Journal ›› 2021, Vol. 49 ›› Issue (7): 699-705.doi: 10.11958/20203042

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The effect of Fushen recipe on peritoneal ultrafiltration function and VEGF-Notch signal pathway in uremic peritoneal dialysis rats

YANG Bo, WANG Meng-meng, SUN Lin, ZHONG Ke, LI Jie, YANG Hong-tao   

  1. 1 Department of Nephrology, the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China; 2 Department of Endocrinology, Fuyang Fourth People's Hospital, Anhui Province
  • Received:2020-11-05 Revised:2021-01-13 Published:2021-07-15 Online:2021-07-12

Abstract: Objective To explore the effects of Fushen recipe on the peritoneal ultrafiltration function and Notch1, delta- like ligand 4 (Dll4), Notch intracellular domain (NICD), hairy and enhancer of split homolog-1 (Hes1), vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) in peritoneal tissues of uremic peritoneal dialysis rats. Methods Fifty male SD rats were randomly divided into 5 groups: normal group, model group, Fushen recipe low dose group (model + Fushen recipe 324 g/L), Fushen recipe high dose group (model + Fushen recipe 648 g/L) and Celecoxib group (model + Celecoxib 1.8 g/L), with 10 rats in each group. The peritoneal dialysis solution was injected intraperitoneally regularly for 4 weeks. The rats were killed after the calculation of ultrafiltration volume by peritoneal balance test. The peritoneal tissues were taken for the observation of morphological changes of peritoneum by HE staining. The mRNA and protein expressions of Notch1, Dll4, NICD, Hes1, VEGF and VEGFR-2 were detected by real-time fluorescence quantitative PCR (qPCR) and Western blot assay, and the protein level of p-VEGFR-2 was detected by Western blot assay. Results The peritoneal ultrafiltration volume was significantly lower in model group, Fushen recipe low-dose group, Fushen recipe high-dose group and Celecoxib group than that in normal group, while the peritoneal ultrafiltration volume was significantly higher in Fushen recipe high-dose group and Celecoxib group than that of model group and Fushen recipe low-dose group. The peritoneal ultrafiltration volume was significantly lower in Celecoxib group than that of Fushen recipe high-dose group (P<0.05). The peritoneal HE staining showed that peritoneal neovascularization was significantly reduced in Fushen recipe low-dose and high-dose groups compared with that in model group. Compared with normal group, the expressions of Notch1, NICD, Dll4, Hes1 mRNA and protein were down-regulated in peritoneal tissue of model group, while the expressions of VEGFR-2, VEGF mRNA and VEGFR-2, p-VEGFR-2 and VEGF protein were significantly up-regulated (P<0.05). Compared with the model group, the expressions of NCID, Hes1 mRNA and Notch1, NICD, Dll4 and Hes1 protein were up-regulated, while the expressions of VEGFR-2, VEGF mRNA and VEGFR-2, p-VEGFR-2 and VEGF protein were down-regulated in the Fushen recipe low-dose group (P<0.05). The expressions of Notch1, NICD, Dll4, Hes1 mRNA and Dll4, Hes1 protein were up-regulated, while the expressions of VEGFR-2, VEGF mRNA and VEGFR-2, p-VEGFR-2, VEGF protein were significantly down-regulated (P<0.05). In Celecoxib group, Notch1 mRNA and Notch1, Dll4 protein were up-regulated, while VEGFR-2 and VEGF mRNA and p-VEGFR2, VEGFR-2 and VEGF protein were significantly down-regulated (P<0.05). Conclusion Fushen recipe can improve peritoneal ultrafiltration function, which may be related to the up-regulation of Notch1, NICD, Dll4, Hes1 mRNA and protein expression in peritoneal tissue, and the down-regulation of VEGFR-2, VEGF mRNA and VEGFR-2, p-VEGFR-2 and VEGF protein expression.

Key words: peritoneal dialysis, uremia, ultrafiltration, vascular endothelial growth factors, receptors, Notch, Fushen recipe, VEGF-Notch signaling pathway