Characterisation of cystathionine gamma-lyase/hydrogen sulphide pathway in ischaemia/reperfusion injury of the mouse kidney: An in vivo study
Characterisation of cystathionine gamma-lyase/hydrogen sulphide pathway in ischaemia/reperfusion injury of the mouse kidney: An in vivo study
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DOI：
10.1016/j.ejphar.2009.01.041
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发表时间：
2009-03-15
影响因子：
5
通讯作者：
Thiemermann, Christoph
中科院分区：
文献类型：
--
作者：
Tripatara, Pinpat;Patel, Nimesh S. A.;Thiemermann, Christoph
内源性硫化氢的产生可能限制或促进由缺血/再灌注损伤引起的组织损伤的程度。在这里，我们试图在小鼠肾缺血/再灌注损伤模型中观察内源性硫化氢合成途径和硫化氢供体硫氢化钠的作用。将体重为20-25 g的麻醉雄性C57/B小鼠分成两组;（i）“缺血/再灌注损伤”，其中通过夹紧肾蒂30分钟然后再灌注24小时对小鼠进行双侧肾缺血，（ii）“假手术”，其中对小鼠进行与上述相同的外科手术，除了肾缺血/再灌注。在实验结束时对肾脏进行的蛋白质印迹分析表明，胱硫醚γ-裂解酶（在心血管系统中负责产生硫化氢的酶）在正常肾脏中表达，并且在缺血/再灌注损伤后显著增加。缺血/再灌注损伤显著增加肾匀浆中硫化氢的产生速率，并增加硫化氢的血浆浓度。此外，我们已经表明，在缺血前30分钟和再灌注6小时给予硫化氢供体硫氢化钠（100 μ mol/kg）可显著减轻缺血/再灌注损伤诱导的肾功能障碍（由血清肌酐和尿素表示）。这些研究结果表明，硫化氢保护肾脏免受缺血/再灌注损伤，并且在缺血/再灌注损伤期间增加胱硫醚γ-裂解酶的表达可能是限制肾缺血/再灌注损伤的许多内源性机制之一。(C)2009 Elsevier B. V.保留所有权利。
The generation of endogenous hydrogen sulphide may either-limit or or contribute to the degree of tissue injury caused by ischaemia/reperfusion injury. Here, we have attempted to characterise the endogenous hydrogen sulphide synthesis pathway and the effects of sodium hydrosulphide, a hydrogen sulphide donor, in a mouse model of renal ischaemia/reperfusion injury. Anaesthetised male C57/b mice weighing 20-25 g were divided into two groups; (i) 'Ischaemia/Reperfusion Injury', in which mice were subjected to bilateral renal ischaemia performed by clamping the renal pedicles for 30 min followed by reperfusion for 24 h, (ii) 'Sham', in which mice were subjected to the same surgical procedures as above, except for renal ischaemia/reperfusion. Western blot analysis of the kidney taken at the end of the experiment demonstrated that cystathionine gamma-lyase, the enzyme responsible for generating hydrogen sulphide in the cardiovascular system, is expressed in the normal kidney and is significantly increased after ischaemia/reperfusion injury. Ischaemia/reperfusion injury significantly increased the rate of hydrogen sulphide production in kidney homogenates and increased the plasma concentration of hydrogen sulphide. In addition, we have shown that administration of the hydrogen sulphide donor sodium hydrosulphide (100 mu mol/kg) 30 min prior to ischaemia and 6 h into reperfusion significantly attenuated ischaemia/reperfusion injury-induced renal dysfunction indicated by serum creatinine and Urea. These findings suggest that hydrogen sulphide protects the kidney against ischaemia/reperfusion injury and that the increase in expression of the enzyme cystathionine gamma-lyase during ischaemia/reperfusion injury may be one of many endogenous mechanisms to limit renal ischaemia/reperfusion injury. (C) 2009 Elsevier B.V. All rights reserved.