Hou Cui-Lan, Wang Ming-Jie, Sun Chen, Huang Yong, Jin Sheng, Mu Xue-Pan, Chen Ying, Zhu Yi-Chun
Research Center on Aging and Medicine, Fudan University, Shanghai Key Laboratory of Bioactive Small Molecules, Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, Shanghai, China.
Oxid Med Cell Longev. 2016;2016:7570489. doi: 10.1155/2016/7570489. Epub 2016 Nov 1.
. The study aimed to examine whether hydrogen sulfide (HS) generation changed in the kidney of the ageing mouse and its relationship with impaired kidney function. . HS levels in the plasma, urine, and kidney decreased significantly in ageing mice. The expression of two known HS-producing enzymes in kidney, cystathionine -lyase (CSE) and cystathionine--synthase (CBS), decreased significantly during ageing. Chronic HS donor (NaHS, 50 mol/kg/day, 10 weeks) treatment could alleviate oxidative stress levels and renal tubular interstitial collagen deposition. These protective effects may relate to transcription factor Nrf2 activation and antioxidant proteins such as HO-1, SIRT1, SOD1, and SOD2 expression upregulation in the ageing kidney after NaHS treatment. Furthermore, the expression of HS-producing enzymes changed with exogenous HS administration and contributed to elevated HS levels in the ageing kidney. . Endogenous hydrogen sulfide production in the ageing kidney is insufficient. Exogenous HS can partially rescue ageing-related kidney dysfunction by reducing oxidative stress, decreasing collagen deposition, and enhancing Nrf2 nuclear translocation. Recovery of endogenous hydrogen sulfide production may also contribute to the beneficial effects of NaHS treatment.
该研究旨在探讨衰老小鼠肾脏中硫化氢(HS)生成是否发生变化及其与肾功能受损的关系。衰老小鼠血浆、尿液和肾脏中的HS水平显著降低。肾脏中两种已知的HS生成酶,胱硫醚 -γ-裂解酶(CSE)和胱硫醚-β-合酶(CBS)的表达在衰老过程中显著下降。慢性HS供体(NaHS,50 μmol/kg/天,10周)治疗可减轻氧化应激水平和肾小管间质胶原沉积。这些保护作用可能与NaHS治疗后衰老肾脏中转录因子Nrf2的激活以及抗氧化蛋白如HO-1、SIRT1、SOD1和SOD2表达上调有关。此外,HS生成酶的表达随外源性HS给药而改变,并导致衰老肾脏中HS水平升高。衰老肾脏中内源性硫化氢生成不足。外源性HS可通过降低氧化应激、减少胶原沉积和增强Nrf2核转位来部分挽救衰老相关的肾功能障碍。内源性硫化氢生成的恢复也可能有助于NaHS治疗的有益效果。