天津医药

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H2S对尿源性脓毒血症肾损伤的影响

许武军1,汪翼1,罗志刚1,罗红梅2,张涛1,刘俊1,陈仙1   

  1. 1. 南华大学附属第二医院泌尿外科
    2. 南华大学组胚教研室
  • 收稿日期:2014-01-14 修回日期:2014-03-30 出版日期:2014-08-15 发布日期:2014-08-15
  • 通讯作者: 许武军

Hydrogen sulfide reduces kidney injury of urinary-derived sepsis by inhibiting NF-κB expression, decreasing TNF-α and increasing IL-10 levels

  • Received:2014-01-14 Revised:2014-03-30 Published:2014-08-15 Online:2014-08-15

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摘要： 【摘要】目的   探讨硫化氢（H2S）对尿源性脓毒血症肾损伤的影响及其机制。 方法   将30只大白兔随机分成Control组；Sham组；sepsis组；NaHS2.8umol/kg组; NaHS8.4umol/kg组，每组6只。建立上尿路急性梗阻并感染脓毒血症动物模型。采血行外周血细胞计数分析(WBC)、肾功能(Cr、BUN）。肾组织光学显微镜及透射电子显微镜观察形态结构变化；应用免疫组织化学法检测肾组织TNF-α、IL-10、NF-κB的蛋白表达；亚甲基蓝分光光度计法测肾组织胱硫醚-γ-裂解酶 (cystathionine-γ-lyase, CSE)的活性，采用去蛋白法测定血浆H2S浓度。 结果   sepsis组WBC、Cr、Bun明显高于control组（P＜0.05），NaHS组WBC、Cr、Bun水平较sepsis组明显下降（P＜0.05）。NaHS组肾病理形态损害较sepsis组改善。sepsis组肾组织TNF-α、IL-10、NF-κB蛋白表达增强(P < 0.05). NaHS 组TNF-α和NF-κB蛋白表达较sepsis组下降，而IL-10表达明显增强 (P < 0.05)。 sepsis组血浆H2S浓度及肾组织CSE活性明显降低(P<0.05)。NaHS 组血浆H2S浓度升高 (P < 0.05)，且NaHS 8.4 umol/kg组较NaHS 2.8umol/kg组升高明显。 结论   内源性硫化氢通过抑制NF-κB的表达，下调TNF-α，上调IL-10，减轻尿源性脓毒血症肾损伤。

关键词: 硫化氢, NF-κB, 肿瘤坏死因子α, 白细胞介素10, 胱硫醚γ裂合酶, 肾损伤, 尿源性脓毒血症

Abstract: [Abstract] Objective    to investigate the effect and mechanism of hydrogen sulfide (H2S) on kidney injury induced by urinary-derived sepsis. Methods   Rabbits were randomly divided into control group, sham group, sepsis group, NaHS 2.8 umol/kg group, and NaHS 8.4 umol/kg group, with 6 rabbits in each group. Upper urinary tract obstruction and acute infection was induced to establish sepsis model. Blood was taken for white blood cell count (WBC), creatinine (Cr) and blood urea nitrogen (BUN) analysis. Morphological changes were observed by HE staining and transmission electron microscopy. Immunohistochemical staining was used to detect TNF-α, IL-10 and NF-κB expression. Cystathionine-γ-lyase (CSE) activity was measured by spectrophotometric methylene blue method and blood H2S concentration by deproteinization. Results   Levels of WBC, Cr and BUN were significantly elevated in sepsis group than control group (P < 0.05). After treatment with NaHS, levels of WBC, Cr and BUN were significantly decreased in NaHS groups than sepsis group (P < 0.05). And pathological features of kidney injury were also alleviated by NaHS. In sepsis group, levels of TNF-α, IL-10 and NF-κB were significantly increased (P < 0.05). In NaHS groups, TNF-α and NF-κB levels were significantly inhibited whereas IL-10 level was significantly increased (P < 0.05). H2S content was significantly decreased in sepsis group whereas significantly increased in NaHS group (P < 0.05). Additionally, NaHS 8.4 umol/kg group had better effect than NaHS 2.8umol/kg group. Conclusion   Exogenous H2S reduced kidney injury of urinary-derived sepsis by inhibiting NF-κB, decreasing TNF-α and increasing IL-10.

Key words: hydrogen sulfide, NF-kappa B, tumor necrosis factor-alpha, interleukin-10, cystathionine gamma-ly?ase, kidney injury, urinary-derived sepsis