Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, the Netherlands.
J Am Soc Nephrol. 2013 Apr;24(5):759-70. doi: 10.1681/ASN.2012030268. Epub 2013 Feb 28.
Hydrogen sulfide (H2S) is an endogenous gasotransmitter with physiologic functions similar to nitric oxide and carbon monoxide. Exogenous treatment with H2S can induce a reversible hypometabolic state, which can protect organs from ischemia/reperfusion injury, but whether cystathionine γ-lyase (CSE), which produces endogenous H2S, has similar protective effects is unknown. Here, human renal tissue revealed abundant expression of CSE, localized to glomeruli and the tubulointerstitium. Compared with wild-type mice, CSE knockout mice had markedly reduced renal production of H2S, and CSE deficiency associated with increased damage and mortality after renal ischemia/reperfusion injury. Treatment with exogenous H2S rescued CSE knockout mice from the injury and mortality associated with renal ischemia. In addition, overexpression of CSE in vitro reduced the amount of reactive oxygen species produced during stress. Last, the level of renal CSE mRNA at the time of organ procurement positively associated with GFR 14 days after transplantation. In summary, these results suggest that CSE protects against renal ischemia/reperfusion injury, likely by modulating oxidative stress through the production of H2S.
硫化氢（H2S）是一种内源性气体递质，其生理功能与一氧化氮和一氧化碳相似。外源性 H2S 处理可诱导可逆的低代谢状态，从而保护器官免受缺血/再灌注损伤，但产生内源性 H2S 的胱硫醚 γ-裂解酶（CSE）是否具有类似的保护作用尚不清楚。本研究显示，人肾组织中 CSE 表达丰富，定位于肾小球和肾小管间质。与野生型小鼠相比，CSE 敲除小鼠的肾脏 H2S 产生明显减少，CSE 缺乏与肾缺血/再灌注损伤后损伤和死亡率增加相关。外源性 H2S 处理可挽救 CSE 敲除小鼠免受肾缺血相关的损伤和死亡率。此外，体外过表达 CSE 可减少应激过程中产生的活性氧的量。最后，器官获取时的肾 CSE mRNA 水平与移植后 14 天的 GFR 呈正相关。综上所述，这些结果表明 CSE 可通过产生 H2S 来调节氧化应激，从而防止肾缺血/再灌注损伤。
