Bozkurt Devrim, Hur Ender, Ulkuden Burcu, Sezak Murat, Nar Hasim, Purclutepe Ozlem, Sen Sait, Duman Soner
Divisions of Nephrology, Ege University, Izmir, Turkey.
Perit Dial Int. 2009 Feb;29 Suppl 2:S202-5.
Long-term use of the peritoneum as a dialysis membrane results in progressive irreversible dysfunction, described as peritoneal fibrosis. Oxidative stress during peritoneal dialysis has been established in many studies. Generation of reactive oxygen species (ROS) by conventional peritoneal dialysis solutions, regardless of whether produced by high glucose, angiotensin II, or glucose degradation products may be responsible for progressive membrane dysfunction. The well-known antioxidant molecule N-acetylcysteine (NAC) is capable of direct scavenging of ROS. The aim of the present study was to investigate the effect of NAC therapy on both progression and regression of encapsulating peritoneal sclerosis (EPS). We divided 49 nonuremic Wistar albino rats into four groups: Control group-2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks; CG group-2 mL/200 g 0.1% chlorhexidine gluconate (CG) and 15% ethanol dissolved in saline injected IP daily for a total of 3 weeks; Resting group-CG (weeks 1 - 3), plus peritoneal resting (weeks 4 - 6); NAC-R group-CG (weeks 1 - 3), plus 2 g/L NAC (weeks 4 - 6). At the end of the experiment, all rats underwent a 1-hour peritoneal equilibration test with 25 mL 3.86% PD solution. Dialysate-to-plasma ratio (D/P) urea, dialysate white blood cell count (per cubic milliliter), ultrafiltration (UF) volume, and morphology changes of parietal peritoneum were examined. The CG group progressed to encapsulating peritoneal sclerosis, characterized by loss of UF, increased peritoneal thickness, inflammation, and ultimately, development of fibrosis. Resting produced advantages only in dialysate cell count; with regard to vascularity and dialysate cell count, NAC was more effective than was peritoneal rest. Interestingly, we observed no beneficial effects of NAC on fibrosis. That finding may be a result of our experimental severe peritoneal injury model. However, decreased inflammation and vascularity with NAC therapy were promising results in regard to membrane protection.
长期将腹膜用作透析膜会导致渐进性不可逆功能障碍,即腹膜纤维化。许多研究已证实腹膜透析过程中存在氧化应激。传统腹膜透析液产生的活性氧(ROS),无论其是由高糖、血管紧张素II还是葡萄糖降解产物产生的,都可能是导致膜功能渐进性障碍的原因。著名的抗氧化分子N-乙酰半胱氨酸(NAC)能够直接清除ROS。本研究的目的是探讨NAC治疗对包裹性腹膜硬化(EPS)进展和逆转的影响。我们将49只非尿毒症Wistar白化大鼠分为四组:对照组——每天腹腔内(IP)注射2 mL等渗盐水,共3周;CG组——每天IP注射2 mL/200 g含0.1%葡萄糖酸氯己定(CG)和15%乙醇的生理盐水,共3周;静息组——CG(第1 - 3周),加上腹膜静息(第4 - 6周);NAC-R组——CG(第1 - 3周),加上2 g/L NAC(第4 - 6周)。实验结束时,所有大鼠用25 mL 3.86%的腹膜透析(PD)溶液进行1小时的腹膜平衡试验。检测透析液与血浆尿素比率(D/P)、透析液白细胞计数(每立方毫米)、超滤(UF)量以及壁层腹膜的形态变化。CG组进展为包裹性腹膜硬化,其特征为超滤丧失、腹膜厚度增加、炎症,最终发展为纤维化。静息仅在透析液细胞计数方面有优势;在血管形成和透析液细胞计数方面,NAC比腹膜静息更有效。有趣的是,我们未观察到NAC对纤维化有有益作用。这一发现可能是由于我们的实验性严重腹膜损伤模型所致。然而,NAC治疗使炎症和血管形成减少,这在膜保护方面是很有前景的结果。