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己酮可可碱与N-乙酰半胱氨酸在肝脏缺血/再灌注损伤中的作用

Pentoxifylline and N-acetylcysteine in hepatic ischemia/reperfusion injury.

作者信息

Demir S, Inal-Erden M

机构信息

Department of Biochemistry, Pamukkale University, The School of Medicine, Denizli, Turkey.

出版信息

Clin Chim Acta. 1998 Jul 28;275(2):127-35. doi: 10.1016/s0009-8981(98)00078-3.

Abstract

This study was designed to clarify the effects of pentoxifylline (PTX) and N-acetylcysteine (NAC) on hepatic reperfusion injury in rats. Rats were pretreated with NAC, or PTX, or combination of the drugs. In each rat, liver was isolated after twenty minutes reperfusion following thirty minutes ischemia. Plasma alanine amino transferase (ALT) activity, liver tissue glutathione (GSH) and malondialdehyde (MDA) levels, glutathione peroxidase (GPx), glutathione reductase (GSSGR), superoxide dismutase (SOD) and catalase (CAT) activities were determined. Plasma ALT activity was higher in ischemia/reperfusion groups than in control. It was decreased in the groups given NAC. Administration of NAC maintained tissue GSH levels, whereas the levels were decreased in both the ischemia/reperfusion groups treated (P < 0.05) and untreated with PTX (P < 0.01). Increases in liver MDA concentration in ischemia/reperfusion (P < 0.01) and PTX-treated groups (P < 0.05) were mitigated by administration of NAC. GPx and CAT activities were increased in the ischemia/reperfusion (P < 0.01, P < 0.05) and PTX-treated groups (P < 0.05, P < 0.001). GSSGR activities were increased in the NAC (P < 0.001) and NAC-PTX-treated groups (P < 0.01). SOD activities were higher in the ischemia/reperfusion (P < 0.01) and the PTX-treated (P < 0.01) and the NAC-PTX-treated groups (P < 0.01 ). In conclusion, short-term liver ischemia/reperfusion diminished GSH, increased MDA and induced some antioxidant enzymes. While we could not find any useful effects with PTX as we expected, our findings indicate that NAC might be useful to prevent tissue damage in hepatic ischemia/reperfusion injury.

摘要

本研究旨在阐明己酮可可碱(PTX)和N-乙酰半胱氨酸(NAC)对大鼠肝脏再灌注损伤的影响。大鼠分别用NAC、PTX或两种药物联合进行预处理。每只大鼠在缺血30分钟后再灌注20分钟,然后分离肝脏。测定血浆丙氨酸氨基转移酶(ALT)活性、肝组织谷胱甘肽(GSH)和丙二醛(MDA)水平、谷胱甘肽过氧化物酶(GPx)、谷胱甘肽还原酶(GSSGR)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性。缺血/再灌注组的血浆ALT活性高于对照组。NAC给药组的ALT活性降低。NAC给药可维持组织GSH水平,而在接受PTX治疗(P<0.05)和未接受PTX治疗(P<0.01)的缺血/再灌注组中,GSH水平均降低。NAC给药减轻了缺血/再灌注组(P<0.01)和PTX治疗组(P<0.05)肝脏MDA浓度的升高。缺血/再灌注组(P<0.01,P<0.05)和PTX治疗组(P<0.05,P<0.001)的GPx和CAT活性升高。NAC组(P<0.001)和NAC-PTX治疗组(P<0.01)的GSSGR活性升高。缺血/再灌注组(P<0.01)、PTX治疗组(P<0.01)和NAC-PTX治疗组(P<0.01)的SOD活性较高。总之,短期肝脏缺血/再灌注会降低GSH水平、增加MDA并诱导一些抗氧化酶。虽然我们没有如预期发现PTX有任何有益作用,但我们的研究结果表明,NAC可能有助于预防肝脏缺血/再灌注损伤中的组织损伤。

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