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Effects of S-Adenosyl-L-Methionine on Liver Damage in Experimental Obstructive Jaundice

S-Adenosyl-L-Methionine對阻塞性黃疸之研究

摘要


S-Adenosyl-L-Methionine (SAMe)乃廣泛分佈於生物體組織內的一種自然物,其在許多生化反應中,可作為甲基族供應者及當做酵素活化劑。在肝臟中,methionine可經由SAMe合成酵素以合成SAMe。於慢性肝疾病時,由於glutathione濃度下降,不足以保護SAMe合成酵素免於受氧化性的傷害,故SAMe合成酵素活性下降。但若於體外補充SAMe,可能會彌補因SAMe酵素活性下降所導致之異常。在本實驗中,我們探討了當皮下注射SAMe後,其對阻塞性黃疸老鼠的肝保護作用之效益評估。結果如下:當大白鼠施以總膽管結紮手術後,呈現不正常的肝功能現象;血中脂質過氧化物濃度增加、還原型麩胱汰組成下降,此結果表示:當罹患阻塞性黃疸時,因膽汁缺乏導致脂溶性維生素吸收不良,影響抗氧化物之抗氧化作用;除此之外,阻塞性黃疸所引起的肝組織傷害中,脂質過氧化作用增加,消耗了體內的抗氧化物,故更加強了氧化性傷害,而SAMe的補充可以改善此種氧化性傷害。同時,罹患阻塞性黃疸的大白鼠,其血液的分枝族氨基酸與芳香族氨基酸的比值下降,此表示肝功能正在惡化,而SAMe的補充可以改善此種惡化現象。總而言之,SAMe的補充可以改善此種阻塞性黃疸所導致的肝臟損傷,表示其具有肝臟保護效益作。

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並列摘要


S-adenosyl-l-methionine (SAMe) is a naturally occurring molecule distributed throughout the body tissues, including the liver. It acts as a methyl group donor and as an enzyme activator in a number of biochemical reactions. Methionine is metabolized in the liver, where it is converted to SAMe by SAMe-synthetase. In patients with liver diseases, these pathways are impaired because of the decreased contents of glutathione, the major abnormality being a reduction in SAMe-synthetase activity. Exogenous SAMe may overcome the results of impaired SAMe-synthetase activities. We conducted this study to evaluate the effect of SAMe administration on liver damage induced by biliary obstruction. Rats with common bile duct ligation exhibited abnormal liver functions, increased lipid peroxide levels,and decreased reduced glutathione contents when compared with the shammed-controls, which indicated that there was oxidative stress in rats with obstructive jaundice; however, SAMe application improved these injuries. There were significant alterations of the levels of amino acid profiles in animals with obstructive jaundice. The ratio between branch chain and aromatic amino acid was depressed, which indicated that the condition of liver was worsening, but SAMe administration improved these alterations significantly. In conclusion, SAMe administration alleviated the liver damage, indicating an important hepatoprotective effect of this methyl donor.

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