Kono Rika, Kanozawa Koichi, Shimosawa Tatsuo, Tayama Yousuke, Matsuda Akihiko, Hasegawa Hajime, Mitarai Tetsuya
Division of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama, 350-8550, Japan,
Clin Exp Nephrol. 2014 Feb;18(1):124-9. doi: 10.1007/s10157-013-0801-0. Epub 2013 Apr 6.
Adrenomedullin (AM) possesses vasodilative and cell-protective properties. Glycine combines with the C-terminal of AM to form mature, physiologically active AM (mAM). AM is reportedly induced by high glucose condition in vascular endothelial or smooth muscle cells; however, little is known on how AM is activated by amidation. To investigate the behavior of AM in patients undergoing peritoneal dialysis (PD), the concentrations of AM, mAM and CA125 were measured. The mAM to AM ratio (mAM/AM ratio) was also evaluated as a marker of amidation activity.
Twenty patients were recruited for this study. The effluent at the time of the peritoneal equilibration test was collected and AM, mAM and CA125 concentrations were measured. The expression of AM in peritoneal mesothelial cells (PMCs) collected from effluent was also examined with an indirect immunofluorescent method.
Mean values of AM and mAM in effluent were 18.1 ± 1.6 and 4.1 ± 0.3 fmol/mL, respectively. In plasma, they were 42.6 ± 3.3 and 5.6 ± 0.6 fmol/mL, respectively. AM concentrations in effluent did not correlate with plasma AM level but correlated well with the dialysate-to-plasma ratio of creatinine (D/P ratio of creatinine). Moreover, in 7 of 20 cases, concentrations of the mAM and mAM/AM ratio in effluent were higher than in plasma. In effluent, AM concentration but not the mAM/AM ratio correlated with CA125 concentration. Immunocytological study revealed diffuse, cytoplasmic expression of AM in PMCs which were collected from effluent during PD.
AM is expressed by PMCs and actively amidated in the abdominal cavity of patients undergoing PD.
肾上腺髓质素（AM）具有血管舒张和细胞保护特性。甘氨酸与AM的C末端结合形成成熟的、具有生理活性的AM（mAM）。据报道，在血管内皮细胞或平滑肌细胞中，高糖条件可诱导AM产生；然而，关于AM如何通过酰胺化被激活的了解甚少。为了研究接受腹膜透析（PD）患者体内AM的情况，我们检测了AM、mAM和CA125的浓度。mAM与AM的比值（mAM/AM比值）也作为酰胺化活性的标志物进行了评估。
本研究招募了20名患者。收集腹膜平衡试验时的流出液，检测AM、mAM和CA125的浓度。还用间接免疫荧光法检测了从流出液中收集的腹膜间皮细胞（PMCs）中AM的表达。
流出液中AM和mAM的平均值分别为18.1±1.6和4.1±0.3 fmol/mL。血浆中它们的平均值分别为42.6±3.3和5.6±0.6 fmol/mL。流出液中AM浓度与血浆AM水平无关，但与肌酐的透析液与血浆比值（肌酐D/P比值）密切相关。此外，在20例中的7例中，流出液中mAM浓度和mAM/AM比值高于血浆。在流出液中，AM浓度与CA125浓度相关，但mAM/AM比值与CA125浓度无关。免疫细胞研究显示，PD期间从流出液中收集的PMCs中AM呈弥漫性细胞质表达。
PMCs可表达AM，并在接受PD患者的腹腔中被积极酰胺化。
