甲醛对大鼠肺细胞醛糖还原酶的影响及醛糖还原酶功能研究Effects of Formaldehyde on Activity of Aldose Reductase in Rat Lung Cells and AR Function Study
杨玉花;袭著革;晁福寰;林本成;张华山;张伟;刘焕亮;杨丹凤;
摘要(Abstract)：
为了研究甲醛作用后大鼠肺细胞醛糖还原酶(AR)的活性变化以及AR在肺细胞损伤中的功能,首先通过大鼠肺细胞分离培养,观察甲醛对大鼠肺细胞AR活性的影响及AR抑制剂——盐酸小檗碱对AR活性的抑制作用;其次通过流式细胞仪检测甲醛及盐酸小檗碱对大鼠肺细胞周期和凋亡的影响.结果表明:1.0mmol·L-1甲醛作用24h使大鼠肺细胞AR活性显著增加,盐酸小檗碱对AR活性具有抑制作用;甲醛能够引起大鼠肺细胞凋亡,使G0/G1和S期的细胞比例下降,G2/M期的细胞比例增加;甲醛和盐酸小檗碱共同作用使大鼠肺细胞凋亡率较单纯甲醛组更高,同时G0/G1期的细胞比例增加,S和G2/M期的细胞比例下降.结果提示甲醛能够使大鼠肺细胞AR活性增加;AR活性增加可减少细胞凋亡,对甲醛引起的大鼠肺细胞损伤具有保护作用.
关键词(KeyWords)： 甲醛;大鼠;肺细胞;醛糖还原酶;细胞凋亡
基金项目(Foundation): 国家“十五”科技攻关计划项目(No.2001BA704B01);; 国家社会公益基金项目(No.2001DA1001)
作者(Author): 杨玉花;袭著革;晁福寰;林本成;张华山;张伟;刘焕亮;杨丹凤;
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参考文献(References)：
- Adams J D,Klaidman L K.1993.Acrolein-induced oxygenradical formation[J].Free Radic Biol Med,15:193-197
- Chandra A,Srivastava S,Petrash J M,Bhatnagar A,Srivastava SK.1997.Active site modification of aldose reductase by nitricoxide donors[J].Biochim Biophys Acta,1341:217
- Choudhary S,Xiao T,Srivastava S,Zhang W,Chan L L,Vergara L A,Van Kuijk F J,Ansari N H.2005.Toxicity anddetoxification of lipid-derived aldehydes in cultured retinal pigmentedepithelial cells[J].Toxicol Appl Pharmacol,204(2):122-134
- Crabbe M J.2003.Aldose reductase and the important ofexperimental design[J].Biochem Soc Trans,31(6):1367-1371
- Doorn J A,Srivastava S K,Petersen D R.2003.Aldosereductase catalyzes reduction of the lipid peroxidation product4-oxonon-2-enal[J].Chem Res Toxicol,16(11):1418-1423
- Huang C Y,Wen G B,Cao R X,Liu J H.2002.Effect ofhigh-d-glucose on cell cycle and apoptosis in cultured vascularendothelial cells[J].Journal of Nanhua University(MedicalEdition),30(4):331-334(in Chinese)
- Keightley J A,Shang L,Kinter M.2004.Proteomics analysis ofoxidative stress-resistant cells:a specific role for aldose reductaseoverexpression in cytoprotection[J].Mol Cell Proteomics,3(2):167-175
- Liu J,Liu H L,Wang G X,Yan Y,Li R,Yang X.2003.Suppression effect of gasous formaldehyde on superoxide dismutase(SOD)of various organs of mice[J].Journal of Environmentand Health,20(2):81-83(in Chinese)
- Okuda Y,Kawashima K,Suzuki S,Asakura Y,Asano M,Tsurumaru K,Dai H,Tachi Y,Bannai C,Saitoh M,YamashitaK.1997.Restoration of nitric oxide production by aldosereductase inhibitor in human endothelial cells,cultured in high-glucose medium[J].Life Sci,60:53
- Ramasamy R.2003.Aldose reductase:a novel target for cardio-protective interventions[J].Curr Drug Targets,4(8):625-632
- Rittner H L,Hafner V,Klimiuk P A,Szweda L I,Goronzy J J,Weyand C M.1999.Aldose reductase functions as a detoxificationsystem for lipid peroxidation products in vasculitis[J].J ClinInvest,103(7):1007-1013
- Ruef J,Liu S Q,Bode C,Tocchi M,Srivastava S,Runge M S,Bhatnagar A.2000.Involvement of aldose reductase in vascularsmooth muscle cell growth and lesion formation after arterialinjury[J].Arteriosclerosis,Thrombosis,and Vascular Biology,20:1745-1753
- Srivastava S,Chandra A,Bhatnagar A,Srivastava S K,Ansari NH.1995.Lipid peroxidation product,4-hydroxynonenal and itsconjugate with GSH are excellent substrates of bovine lens aldosereductase[J].Biochem Biophys Res Comm,217(3):741-746
- Srivastava S,Spite M,Trent J O,West M B,Ahmed Y,Bhatnagar A.2004.Aldose reductase-catalyzed reduction of aldehydephospholipids[J].J Biol Chem,279(51):53395-53406
- Yang Y H,Xi Z G,Chao F H,Lin B C,Zhang H S,ZhangW.2007.Pathological effects of formaldehyde inhalation on lungof rats[J].Asian Journal of Ecotoxicology,2(3):303-307(inChinese)
- Yang Y H,Xi Z G,Chao F H,Yang D F.2005.Effects offormaldehyde Inhalation on lung of rat[J].Biomed Environ Sci,18(3):164-168
- Zhang J T.1998.Empirical Method of Modern Pharmacology[M].Beijing:Associated Press of Beijing Medical University andPeking Union Medical College.993-994(in Chinese)
- 黄雌友,文格波,曹仁贤,刘江华.2002.葡萄糖对人血管内皮细胞周期和凋亡的影响[J].南华大学学报·医学版,30(4):331-334
- 刘杰,刘宏亮,王光学,严彦,李睿,杨旭.2003.气态甲醛对小鼠不同组织器官SOD的抑制作用[J].环境与健康杂志,20(2):81-83
- 杨玉花,袭著革,晁福寰,林本成,张华山,张伟.2007.气态甲醛对大鼠肺组织影响的病理学观察[J].生态毒理学报,2(3):310-314
- 张均田.1998.现代药理学实验方法[M].北京:北京医科大学和中国协和医科大学出版社.993-994