Mondello Stefania, Mazzon Emanuela, Di Paola Rosanna, Crisafulli Concetta, Mondello Paolo, Buemi Michele, Aloisi Carmelo, Cuzzocrea Salvatore
Department of Internal Medicine, Messina University Hospital, School of Medicine, University of Messina, Messina, Italy.
Shock. 2009 Sep;32(3):332-9. doi: 10.1097/SHK.0b013e3181994974.
Peritoneal dialysis is an alternative treatment of patients with end-stage renal disease. Sclerosing encapsulating peritonitis is a life-threatening complication of continuous ambulatory peritoneal dialysis. The aim of the present study was to evaluate the effect of thalidomide, which is used for the treatment of various inflammatory and autoimmune diseases, on the development of sclerosing encapsulating peritonitis induced by chlorhexidine gluconate (CG). A peritoneal fibrosis model was established using rats treated intraperitoneally with injections of CG. Thalidomide was administered orally at a dose of 100 mg/kg three times per week. When compared with CG-treated rats, thalidomide (100 mg/kg orally)-treated mice subjected to CG-induced peritoneal fibrosis experienced a significantly lower rate in the extent and severity of histological signs of peritoneal injury. Thalidomide also caused a substantial reduction of 1) the rise in myeloperoxidase activity (mucosa); 2) the expression in the tissue of TNF-alpha, IL-1beta, transforming growth factor-beta, and vascular endothelial growth factor; 3) the increase in staining (immunohistochemistry) for nitrotyrosine and for poly(ADP ribose), as well as 4) the nuclear factor-kappaB activation caused by CG in the peritoneum. Thus, thalidomide treatment reduces the degree of peritoneal fibrosis caused by CG. We propose that this evidence may help clarify the potential therapeutic actions of thalidomide in patients with peritoneal fibrosis.
腹膜透析是终末期肾病患者的一种替代治疗方法。硬化性包裹性腹膜炎是持续性非卧床腹膜透析的一种危及生命的并发症。本研究的目的是评估用于治疗各种炎症和自身免疫性疾病的沙利度胺对葡萄糖酸氯己定（CG）诱导的硬化性包裹性腹膜炎发展的影响。使用腹腔注射CG处理的大鼠建立腹膜纤维化模型。沙利度胺以100mg/kg的剂量每周口服三次给药。与CG处理的大鼠相比，接受CG诱导的腹膜纤维化的沙利度胺（口服100mg/kg）处理的小鼠腹膜损伤组织学征象的程度和严重程度发生率显著降低。沙利度胺还使以下各项大幅降低：1）髓过氧化物酶活性（黏膜）升高；2）肿瘤坏死因子-α、白细胞介素-1β、转化生长因子-β和血管内皮生长因子在组织中的表达；3）硝基酪氨酸和聚（ADP核糖）染色（免疫组织化学）增加，以及4）CG在腹膜中引起的核因子-κB激活。因此，沙利度胺治疗可减轻CG引起的腹膜纤维化程度。我们认为，这一证据可能有助于阐明沙利度胺对腹膜纤维化患者的潜在治疗作用。
