【摘要】目的探討一氧化氮(NO)在大鼠梗阻性黃疸腎功能損害發(fā)生中的作用,以及褪黑素(melatonin,Mel)的保護(hù)作用。
方法64只雄性SD大鼠隨機(jī)均分為4組: 正常對(duì)照組(CN組)、假手術(shù)組(SO組)、膽總管結(jié)扎組(BLD組)和褪黑素治療組(BDL+Mel組)。應(yīng)用膽總管結(jié)扎法建立梗阻性黃疸模型,分別于手術(shù)后第4天和第8天兩個(gè)時(shí)間點(diǎn)檢測4組中血漿NO、TB、DB、ALT、AST、BUN、Cr水平以及腎組織中NO水平和iNOS活性; 光鏡下觀察腎組織病理形態(tài)改變。
結(jié)果BDL組大鼠血漿NO、TB、DB、ALT、AST、BUN、Cr水平和腎組織NO水平及iNOS活性明顯升高(P<0.01),褪黑素治療可使血漿NO、ALT、AST、BUN及Cr水平和腎組織中NO水平及iNOS活性顯著降低,與BDL組比較差異有顯著性意義(P<0.01)。
結(jié)論梗阻性黃疸時(shí),腎組織iNOS活性增強(qiáng),NO大量產(chǎn)生參與了腎功能損害的發(fā)生、發(fā)展; 褪黑素對(duì)大鼠梗阻性黃疸腎損害的保護(hù)作用至少部分是通過干擾NO通路實(shí)現(xiàn)的。
引用本文: 張小明,寇治民,康二虎,張有成. 褪黑素對(duì)大鼠梗阻性黃疸腎損害的保護(hù)作用. 中國普外基礎(chǔ)與臨床雜志, 2005, 12(1): 55-58. doi: 復(fù)制
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4. | Crespo E, Macias M, Pozo D, et al. Melatonin inhibits expression of the inducible NO synthase II in liver and lung and prevents endotoxemia in lipopolysaccharideinduced multiple organ dysfunction syndrome in rats [J]. FASEB J, 1999; 13(12)∶1537. |
5. | Dugo L, Serraino I, Fulia F, et al. Effect of melatonin on cellular energy depletion mediated by peroxynitrite and poly (ADPribose) synthetase activation in an acute model of inflammation [J]. J Pineal Res, 2001; 31(1)∶76. |
6. | Nath KA, Norby SM. Reactive oxygen species and acute renal failure [J].Am J Med, 2000; 109(8)∶ 665. |
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8. | Jaeschke H. Reactive oxygen and mechanisms of inflammatory liver injury [J].J Gastroenterol Hepatol, 2000; 15(7)∶718. |
9. | Ohta Y, Kongo M, Kishikawa T. Melatonin exerts a therapeutic effect on cholestatic liver injury in rats with bile duct ligation [J]. J Pineal Res, 2003; 34(2)∶119. |
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- 1. GonzalezCorrea JA, De La Cruz JP, MartinAurioles E, et al. Effects of SadenosylLmethionine on hepatic and renal oxidative stress in an experimental model of acute biliary obstruction in rats [J]. Hepatology, 1997; 26(1)∶121.
- 2. 劉祥德, 李衛(wèi),何振平,等. NO與梗阻性黃疸時(shí)腎損害的關(guān)系 [J]. 第二軍醫(yī)大學(xué)學(xué)報(bào), 2001; 23(7)∶795.
- 3. Gilad E, Wong HR, Zingarelli B, et al. Melatonin inhibits expression of the inducible isoform of nitric oxide synthase in murine macrophages: role of inhibition of NFkappaB activation [J]. FASEB J, 1998; 12(9)∶685.
- 4. Crespo E, Macias M, Pozo D, et al. Melatonin inhibits expression of the inducible NO synthase II in liver and lung and prevents endotoxemia in lipopolysaccharideinduced multiple organ dysfunction syndrome in rats [J]. FASEB J, 1999; 13(12)∶1537.
- 5. Dugo L, Serraino I, Fulia F, et al. Effect of melatonin on cellular energy depletion mediated by peroxynitrite and poly (ADPribose) synthetase activation in an acute model of inflammation [J]. J Pineal Res, 2001; 31(1)∶76.
- 6. Nath KA, Norby SM. Reactive oxygen species and acute renal failure [J].Am J Med, 2000; 109(8)∶ 665.
- 7. Kannan K, Jain SK. Oxidative stress and apoptosis [J].Pathophysiology, 2000; 7(3)∶153.
- 8. Jaeschke H. Reactive oxygen and mechanisms of inflammatory liver injury [J].J Gastroenterol Hepatol, 2000; 15(7)∶718.
- 9. Ohta Y, Kongo M, Kishikawa T. Melatonin exerts a therapeutic effect on cholestatic liver injury in rats with bile duct ligation [J]. J Pineal Res, 2003; 34(2)∶119.
- 10. Cruz A, Padillo FJ, Tunez I, et al. Melatonin protects against renal oxidative stress after obstructive jaundice in rats [J]. Eur J Pharmacol, 2001; 425(2)∶135.
- 11. Chen CY, Shiesh SC, Tsao HC, et al. Protective effect of melatonin on renal injury of rats induced by bile duct ligation [J].Dig Dis Sci, 2001; 46(4)∶927.