Tayama Yosuke, Hasegawa Hajime, Takayanagi Kaori, Matsuda Akihiko, Shimizu Taisuke, Asakura Juko, Iwashita Takatsugu, Ogawa Tomonari, Katoh Hitoshi, Mitarai Tetsuya
Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Saitama - Japan.
J Nephrol. 2013 Nov-Dec;26(6):1160-9. doi: 10.5301/jn.5000306. Epub 2013 Nov 26.
Bacterial peritonitis in patients undergoing peritoneal dialysis (PD) is a major cause of therapy interruption due to peritoneal insufficiency. Here we studied the effect of a selective mineralocorticoid receptor (MR) blocker, eplerenone, on the prevention of peritoneal damage.
METHODS: Male Sprague-Dawley rats were treated with a daily infusion of human use PD solution (100 mL/kg i.p., PD group, n = 5), or with PD solution and intermittent intraperitoneal injections of lipopolysaccharide (LPS group, n = 5) or with LPS and eplerenone (100 mg/ kg/d, po, Ep group, n = 5) for 4 weeks. Peritoneal samples were subjected to assessment following the peritoneal equilibration test (PET).
RESULTS: Histological observations revealed that LPS treatment resulted in significant peritoneal thickening associated with increased ED-1-positive cell infiltration and the number of transforming growth factor (TGF)-β1-positive cells, and that eplerenone reduced these changes. LPS administration also evoked significant upregulation of monocyte chemotactic protein-1 and TGF-β1, which were inhibited by eplerenone. PET revealed that ultrafiltration and transperitoneal osmotic diffusion were significantly impaired by LPS and restored by eplerenone. Increased value of the mass transfer area coefficients for creatinine values was also recovered by Ep (0.10 ± 0.01 in the PD, 0.14 ± 0.02 in the LPS and 0.08 ± 0.0 in the Ep groups). Immunostaining for von Willebrand factor showed a significant increase by LPS and its restoration by Ep.
Ep effectively diminished LPS-induced peritoneal insufficiency. A selective blockade of MR might prevent peritoneal insufficiency associated with bacterial peritonitis.
腹膜透析（PD）患者发生细菌性腹膜炎是因腹膜功能不全导致治疗中断的主要原因。在此，我们研究了选择性盐皮质激素受体（MR）阻滞剂依普利酮对预防腹膜损伤的作用。
将雄性Sprague-Dawley大鼠每日腹腔注射人用腹膜透析液（100 mL/kg，腹腔注射，PD组，n = 5），或注射腹膜透析液并间歇性腹腔注射脂多糖（LPS组，n = 5），或注射脂多糖和依普利酮（100 mg/kg/d，口服，Ep组，n = 5），持续4周。在腹膜平衡试验（PET）后对腹膜样本进行评估。
组织学观察显示，LPS治疗导致腹膜显著增厚，伴有ED-1阳性细胞浸润增加和转化生长因子（TGF）-β1阳性细胞数量增多，而依普利酮减轻了这些变化。LPS给药还引起单核细胞趋化蛋白-1和TGF-β1显著上调，依普利酮可抑制这些上调。PET显示，LPS显著损害超滤和经腹膜渗透扩散，而依普利酮可使其恢复。Ep组肌酐值的传质面积系数增加值也恢复正常（PD组为0.10±0.01，LPS组为0.14±0.02，Ep组为0.08±0.0）。血管性血友病因子免疫染色显示，LPS使其显著增加，而Ep可使其恢复。
Ep有效减轻LPS诱导的腹膜功能不全。选择性阻断MR可能预防与细菌性腹膜炎相关的腹膜功能不全。
