Second Department of Internal Medicine, Nagasaki University School of Medicine.
Acta Histochem Cytochem. 2011 Apr 28;44(2):51-60. doi: 10.1267/ahc.10030. Epub 2011 Apr 21.
Thalidomide is clinically recognized as a therapeutic agent for multiple myeloma and has been known to exert anti-angiogenic actions. Recent studies have suggested the involvement of angiogenesis in the progression of peritoneal fibrosis. The present study investigated the effects of thalidomide on the development of peritoneal fibrosis induced by injection of chlorhexidine gluconate (CG) into the mouse peritoneal cavity every other day for 3 weeks. Thalidomide was given orally every day. Peritoneal tissues were dissected out 21 days after CG injection. Expression of CD31 (as a marker of endothelial cells), proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), α-smooth muscle actin (as a marker of myofibroblasts), type III collagen and transforming growth factor (TGF)-β was examined using immunohistochemistry. CG group showed thickening of the submesothelial zone and increased numbers of vessels and myofibroblasts. Large numbers of VEGF-, PCNA-, and TGF-β-positive cells were observed in the submesothelial area. Thalidomide treatment significantly ameliorated submesothelial thickening and angiogenesis, and decreased numbers of PCNA- and VEGF-expressing cells, myofibroblasts, and TGF-β-positive cells. Moreover, thalidomide attenuated peritoneal permeability for creatinine, compared to the CG group. Our results indicate the potential utility of thalidomide for preventing peritoneal fibrosis.
沙利度胺被临床确认为多发性骨髓瘤的治疗药物，具有抗血管生成作用。最近的研究表明，血管生成参与了腹膜纤维化的进展。本研究探讨了沙利度胺对每隔一天向小鼠腹腔内注射葡萄糖酸洗必泰（CG）3 周诱导的腹膜纤维化发展的影响。沙利度胺每天口服给药。CG 注射后 21 天取出腹膜组织。用免疫组织化学法检测 CD31（内皮细胞标志物）、增殖细胞核抗原（PCNA）、血管内皮生长因子（VEGF）、α-平滑肌肌动蛋白（成肌纤维细胞标志物）、III 型胶原和转化生长因子（TGF）-β的表达。CG 组表现为亚膜下区增厚，血管和肌成纤维细胞数量增加。在亚膜下区观察到大量 VEGF、PCNA 和 TGF-β阳性细胞。沙利度胺治疗可显著改善亚膜下增厚和血管生成，并减少 PCNA 和 VEGF 表达细胞、肌成纤维细胞和 TGF-β阳性细胞的数量。此外，与 CG 组相比，沙利度胺可降低腹膜对肌酐的通透性。我们的结果表明沙利度胺在预防腹膜纤维化方面具有潜在的应用价值。
