Hydrogen sulfide as an endogenous modulator of biliary bicarbonate excretion in the rat liver
Hydrogen sulfide as an endogenous modulator of biliary bicarbonate excretion in the rat liver
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DOI：
10.1089/ars.2005.7.788
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发表时间：
2005-05-01
影响因子：
6.6
通讯作者：
Suematsu, M
中科院分区：
文献类型：
--
作者：
Fujii, K;Sakuragawa, T;Suematsu, M
半胱硫氨酸伽马裂解酶是一种催化半胱氨酸和半胱氨酸分别生成半胱氨酸和硫化氢的酶(H2 S).本研究旨在探讨该酶产生的H、S是否可作为肝胆功能的内源性调节因子。气相色谱分析表明，在所研究的大鼠器官中，肝脏是H，S世代在体内的最大成分之一，其含量为100mU/g组织，与肾脏相当，是脑的1.5倍。以前曾报道过肝脏在神经传递调节中的作用。肝脏中至少有一半的气体似乎来自CSE，因为丙氨酸甘氨酸阻断这种酶可以抑制50%。免疫组织化学显示CSE不仅存在于肝细胞，也存在于胆管。在体内的肝脏中，以及在体外灌流的肝脏中，CSE抑制剂的治疗通过刺激胆汁样本中碳酸氢盐的基础排泄来诱导胆汁排泄。门静脉注射30mU·mol/L的NaHS，但不以N-乙酰半胱氨酸为半胱氨酸供体，可阻断CSE抑制剂在肝脏灌流后引起的上述改变。CSE阻断引起的变化与肝脏血管阻力的变化不一致，表明气体的血管扩张效应几乎没有参与这些事件。这些结果首次提供了证据，证明通过CSE产生的H，S调节胆汁重碳酸盐的排泄，因此是大鼠肝脏胆盐非依赖性胆汁形成的决定因素。
Cystathionine gamma-lyase (CSE) is an enzyme catalyzing cystathionine and cysteine to yield cysteine and hydrogen sulfide (H 2 S), respectively. This study aimed to examine if H,S generated from the enzyme could serve as an endogenous regulator of hepatobiliary function. Gas chromatographic analyses indicated that, among rat organs herein examined, liver constituted one of the greatest components of H,S generation in the body, at 100 mu mol/g of tissue, comparable to that in kidney and 1.5-fold greater than that in brain, where roles of the gas in the regulation of neurotransmission were reported previously. At least half of the gas amount in the liver appeared to be derived from CSE, because blockade of the enzyme by propargylglycine suppressed it by 50%. Immunohistochemistry revealed that CSE occurs not only in hepatocytes, but also in bile duct. In livers in vivo, as well as in those perfused ex vivo, treatment with the CSE inhibitor induced choleresis by stimulating the basal excretion of bicarbonate in bile samples. Transportal supplementation of NaHS at 30 mu mol/L, but not that of N-acetylcysteine as a cysteine donor, abolished these changes elicited by the CSE inhibitor in the perfused liver. The changes elicited by the CSE blockade did not coincide with alterations in hepatic vascular resistance, showing little involvement of vasodilatory effects of the gas in these events, if any. These results first provided evidence that H,S generated through CSE modulates biliary bicarbonate excretion and is thus a determinant of bile salt-independent bile formation in the rat liver.