Role of hydrogen sulphide in haemorrhagic shock in the rat: protective effect of inhibitors of hydrogen sulphide biosynthesis
Role of hydrogen sulphide in haemorrhagic shock in the rat: protective effect of inhibitors of hydrogen sulphide biosynthesis
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DOI：
10.1038/sj.bjp.0706014
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发表时间：
2004-12-01
影响因子：
7.3
通讯作者：
Moore, PK
中科院分区：
文献类型：
--
作者：
Mok, YYP;Atan, MSBM;Moore, PK
1 麻醉大鼠失血性休克（60 分钟）导致平均动脉血压 (MAP) 和心率 (HR) 长期下降。2 使用胱硫醚 γ 裂解酶 (CSE；将半胱氨酸转化为硫化氢 (H2S)) 抑制剂进行预处理（休克前 30 分钟）或治疗后（休克后 60 分钟）， dl-炔丙基甘氨酸或β-氰基丙氨酸（50 mg kg(-1)，静脉注射）或格列本脲（40 mg kg(-1)，腹腔注射）可使MAP和HR快速部分恢复。生理盐水和 DMSO 均不影响 MAP 或 HR。3 抽血后 60 分钟血浆 H,S 浓度升高（37.5 +/- 1.3 mum，11 = 18 c.f. 28.9 +/- 1.4 mum，n = 15，P < 0.05）。4 抽血 60 分钟后处死动物制备的肝脏（而非肾脏）匀浆将半胱氨酸转化为 H2S显着增加（52.1 +/- 1.6 立方英尺39.8 +/- 4.1 nmol mg 蛋白质(-1)，n = 8，P < 0.05)，肝脏 CSE mRNA (2.7x) 也是如此。 PAG (IC50, 55.0 +/- 3.2 mum) 和 BCA (IC50, 6.5 +/- 1.2 mum) 均抑制体外肝脏 H2S 合成活性。5 用 PAG 或 BCA（50 mg kg(-1)，腹腔注射）而非格列本脲（40 mg kg(-1)，腹腔注射，K-ATP 通道抑制剂）预处理动物可消除 H2S 的升高。 暴露于失血性休克 60 分钟的动物体内的血浆 H2S 会阻止肝脏中半胱氨酸增强的 H2S 生物合成。6 这些结果表明，H2S 在大鼠失血性休克中发挥作用。 CSE抑制剂可能为失血性休克的治疗提供一种新方法。
1 Haemorrhagic shock (60 min) in the anaesthetized rat resulted in a prolonged fall in the mean arterial blood pressure (MAP) and heart rate (HR).2 Pre-treatment (30 min before shock) or post-treatment (60 min after shock) with inhibitors of cystathionine gamma lyase (CSE; converts cysteine into hydrogen sulphide (H2S)), dl-propargylglycine or beta-cyanoalanine (50 mg kg(-1), i.v.), or glibenclamide (40 mg kg(-1), i.p.), produced a rapid, partial restoration in MAP and HR. Neither saline nor DMSO affected MAP or HR.3 Plasma H,S concentration was elevated 60 min after blood withdrawal (37.5 +/- 1.3 mum, 11 = 18 c.f. 28.9 +/- 1.4 mum, n = 15, P < 0.05).4 The conversion of cysteine to H2S by liver (but not kidney) homogenates prepared from animals killed 60 min after withdrawal of blood was significantly increased (52.1 +/- 1.6 c.f. 39.8 +/- 4.1 nmol mg protein(-1), n = 8, P < 0.05), as was liver CSE mRNA (2.7x). Both PAG (IC50, 55.0 +/- 3.2 mum) and BCA (IC50, 6.5 +/- 1.2 mum) inhibited liver H2S synthesizing activity in vitro.5 Pre-treatment of animals with PAG or BCA (50 mg kg(-1), i.p.) but not glibenclamide (40 mg kg(-1), i.p., K-ATP channel inhibitor) abolished the rise in plasma H2S in animals exposed to 60 min haemorrhagic shock and prevented the augmented biosynthesis of H2S from cysteine in liver.6 These results demonstrate that H2S plays a role in haemorrhagic shock in the rat. CSE inhibitors may provide a novel approach to the treatment of haemorrhagic shock.