Yilmaz Mahmut Ilker, Korkmaz Ahmet, Kaya Ayper, Sonmez Alper, Caglar Kayser, Topal Turgut, Eyileten Tayfun, Yenicesu Mujdat, Acikel Cengizhan, Oter Sukru, Yaman Halil, Aktug Huseyin, Oguz Yusuf, Vural Abdulgaffar, Ikizler T Alp
Department of Nephrology, Gulhane School of Medicine, Etlik-Ankara, Turkey.
Nephron Exp Nephrol. 2006;104(1):e15-22. doi: 10.1159/000093260. Epub 2006 May 11.
BACKGROUND/AIMS: Proteinuria is associated with oxidant stress and inflammation. Hyperbaric oxygen (HBO) treatment has anti-inflammatory and anti-oxidant effects. The aim of the study was to investigate the benefits of HBO treatment on an experimental nephrotic syndrome model.
50 male Sprague-Dawley rats weighing 255 +/- 39 g were housed. Forty rats were injected 6 mg/kg adriamycin into tail veins under anesthesia to induce nephrosis, while 10 rats were spared as sham control. After the stabilization of proteinuria at the sixth week, the rats were treated for 6 weeks by losartan (n = 10, 30 mg/kg/day), HBO (n = 10, 2.8 atmosphere absolute, 90 min/day), HBO + losartan (n = 10) and vehicle (n = 10). Protein carbonyl (PCO), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were analyzed from tissue specimens. Biochemical markers were studied from venous samples and 24-hour urine was collected for proteinuria. The surviving animals at 12 weeks (vehicle group (n = 6), HBO (n = 6), losartan (n = 8), HBO + losartan (n = 10) were sacrificed. Glomerular sclerosis, tubulointerstitial and blood vessel changes were determined by semiquantitative scoring.
The PCO levels increased (p < 0.001), and the GPx and SOD levels decreased (p < 0.001 for both) in the nephrotic rats. In losartan and HBO groups GPx levels increased (p = 0.001, p = 0.002 respectively), but PCO and SOD levels did not change. The combination of HBO with losartan significantly increased the GPx and SOD levels (p = 0.001 for both) and decreased PCO levels (p = 0.005). HBO but not losartan significantly reduced proteinuria (p < 0.001). The combination of HBO and losartan reduced proteinuria better than the single losartan regime (p < 0.001). The effect of the combination was also noticed on the histological examination of the kidneys. The activities, appetites, weight gains, and improvement of edema were better in the HBO combined with losartan regime.
These results indicate that the addition of HBO therapy to a conventional regime, angiotensin receptor blockers, has significant benefits in the management of proteinuria. Future clinical studies are needed to elucidate the role of HBO and other antioxidant strategies in the treatment of proteinuria.
背景/目的：蛋白尿与氧化应激和炎症相关。高压氧（HBO）治疗具有抗炎和抗氧化作用。本研究旨在探讨HBO治疗对实验性肾病综合征模型的益处。
将50只体重255±39 g的雄性Sprague-Dawley大鼠饲养起来。40只大鼠在麻醉下经尾静脉注射6 mg/kg阿霉素以诱导肾病，10只大鼠作为假手术对照。在第6周蛋白尿稳定后，大鼠分别接受氯沙坦（n = 10，30 mg/kg/天）、HBO（n = 10，2.8绝对大气压，90分钟/天）、HBO + 氯沙坦（n = 10）和赋形剂（n = 10）治疗6周。从组织标本中分析蛋白质羰基（PCO）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）。从静脉样本中研究生化标志物，并收集24小时尿液检测蛋白尿。处死12周时存活的动物（赋形剂组（n = 6）、HBO组（n = 6）、氯沙坦组（n = 8）、HBO + 氯沙坦组（n = 10））。通过半定量评分确定肾小球硬化、肾小管间质和血管变化。
肾病大鼠的PCO水平升高（p < 0.001），GPx和SOD水平降低（两者均p < 0.001）。氯沙坦组和HBO组的GPx水平升高（分别为p = 0.001，p = 0.002），但PCO和SOD水平未改变。HBO与氯沙坦联合使用显著提高了GPx和SOD水平（两者均p = 0.001），并降低了PCO水平（p = 0.005）。HBO而非氯沙坦显著降低了蛋白尿（p < 0.001）。HBO与氯沙坦联合使用比单一氯沙坦治疗能更好地降低蛋白尿（p < 0.001）。联合治疗对肾脏组织学检查也有效果。HBO与氯沙坦联合治疗组的活动、食欲、体重增加和水肿改善情况更好。
这些结果表明，在传统治疗方案（血管紧张素受体阻滞剂）基础上加用HBO治疗在蛋白尿管理方面具有显著益处。未来需要进行临床研究以阐明HBO和其他抗氧化策略在蛋白尿治疗中的作用。
