Lu Ying, Gao Luyan, Li Lingyun, Zhu Ye, Wang Zhi, Shen Huaying, Song Kai
Nephron. 2015;131(3):210-9. doi: 10.1159/000441504. Epub 2015 Nov 4.
BACKGROUND/AIMS: Peritoneal fibrosis is one of the long-term complications in peritoneal dialysis (PD) patients. Recent evidences have suggested that hydrogen sulfide (H2S) is beneficial in treating various fibrotic diseases, including pulmonary fibrosis, cirrhosis, kidney fibrosis and cardiac hypertrophy. However, no information is known about the effect of H2S on peritoneal fibrosis. In the present study, we investigated the effect of H2S on peritoneal fibrosis and explored its potential mechanisms.
We developed a model of peritoneal fibrosis by intraperitoneally injecting 4.25%-glucose PD fluids and lipopolysaccharide to Sprague-Dawley rats. The rats received daily intraperitoneal injections of NaHS (56 μg/kg), an H2S donor. After 28 days, the peritoneal equilibration test (PET) was used to assess peritoneal function. At the end of dialysis, the rats were killed and parietal peritoneum was harvested for microscopic examination and immunohistochemistry.
On the 28th day, the parietal peritoneum of the PD rats markedly thickened as a result of increased depositions of type III collagen and fibronectin. Moreover, the number of ED-1-positive cells and the expressions of monocyte chemoattractant protein-1, transforming growth factor-β1 (TGF-β1), α-smooth muscle actin and CD31 were significantly increased in the fibrotic peritoneum. Administration of NaHS markedly decreased the biomarkers of inflammation, fibrosis and angiogenesis in the peritoneum. NaHS also improved peritoneal function assessed by PET.
Exogenous H2S ameliorates the pathologic process of peritonitis via attenuating inflammatory events and TGF-β1 synthesis. These results suggest that H2S may be a potential therapy against peritoneal fibrosis during chronic PD. In the future, compounds releasing H2S at controlled rate will be assessed as potential candidates to treat peritoneal fibrosis.
背景/目的：腹膜纤维化是腹膜透析（PD）患者的长期并发症之一。最近有证据表明，硫化氢（H2S）对治疗各种纤维化疾病有益，包括肺纤维化、肝硬化、肾纤维化和心脏肥大。然而，关于H2S对腹膜纤维化的影响尚无相关信息。在本研究中，我们研究了H2S对腹膜纤维化的影响并探讨了其潜在机制。
我们通过向Sprague-Dawley大鼠腹腔内注射4.25%葡萄糖腹膜透析液和脂多糖建立腹膜纤维化模型。大鼠每天接受腹腔注射NaHS（56μg/kg），一种H2S供体。28天后，采用腹膜平衡试验（PET）评估腹膜功能。透析结束时，处死大鼠并收集壁层腹膜进行显微镜检查和免疫组织化学分析。
在第28天，由于III型胶原和纤连蛋白沉积增加，PD大鼠的壁层腹膜明显增厚。此外，纤维化腹膜中ED-1阳性细胞数量以及单核细胞趋化蛋白-1、转化生长因子-β1（TGF-β1）、α-平滑肌肌动蛋白和CD31的表达显著增加。给予NaHS可显著降低腹膜中炎症、纤维化和血管生成的生物标志物水平。NaHS还改善了通过PET评估的腹膜功能。
外源性H2S通过减轻炎症反应和TGF-β1合成改善腹膜炎的病理过程。这些结果表明，H2S可能是慢性腹膜透析期间对抗腹膜纤维化的一种潜在治疗方法。未来，将评估以可控速率释放H2S的化合物作为治疗腹膜纤维化的潜在候选物。
