唐宗怀,胡韵,秦建国
TANG Zonghuai1,HU Yun2,QIN Jianguo3(1.Anhui Provincial Red-cross Tongling Hospital

• 1:安徽省红十字铜陵医院
• 2:贵阳医学院附院外科
• 3:解放军第44医院肝胆外科 安徽铜陵244000
• 4:贵州贵阳550004

摘要(Abstract)：

目的:探讨一氧化氮合酶(NOS)在梗阻性黄疸大鼠肝脏中的表达及意义。方法:40只雄性W istar大鼠随机分成4组。(1)假手术组(仅游离胆总管);(2)胆总管结扎组;(3)胆总管结扎DAHP干预组(术后腹腔注射DAHP);(4)胆总管结扎L-NAME干预组(术后腹腔注射L-AME)。术后第7天检测TB IL、ALT、AST,NO2-/NO3-、NOS活性,观察肝组织病理改变、eNOS mRNA、iNOS mRNA表达和分布。结果:胆总管结扎组iN-OS活性、NO2-/NO3-、ALT、AST升高,eNOS活性下降;胆总管结扎DAHP干预组和胆总管结扎L-NAME干预组iNOS活性、NO2-/NO3-浓度较低,胆总管结扎L-NAME干预组eNOS活性降低更明显,ALT和AST显著升高;胆总管结扎DAHP干预组eNOS活性未见下降,ALT和AST却明显降低。结扎各组iNOS mRNA阳性表达颗粒增多,eNOS mRNA未见差异。胆总管结扎L-NAME干预组镜下肝损害最重、胆总管结扎DAHP干预组肝损害较轻、假手术组未见肝损害。结论:肝组织iNOS高表达是造成梗阻性黄疸肝损害的主要病理生理机制之一。
Objective: To investigate the expression of nitric oxide synthase(NOS) in the liver of rats with obstructive jaundice and its significance.Methods: Forty male Wistar rats were randomly divided into four groups: Group1(sham operation group),group 2(rats received choledochus ligation only),group 3 [rats received 2,4-diamino-6-hydroxy-pyrimidine(DAHP) intraperitoneally after choledochus ligation],and group 4 [rats received intraperitoneally NG-nitric-L-arginine-methyl ester(L-NAME) after choledochus ligation].All animals were sacrificed on the seventh day and blood samples were taken for the determination of the levels of bilirubin,alanine aminotransferase(ALT) and aspartate aminotransferase(AST).The hepatic contents of NO-2/NO-3 and nitric oxide synthase activity were measured.Besides,liver tissue was collected to localize the expression and distribution of endothelial NOS(eNOS) mRNA and induced NOS(iNOS) mRNA by in situ hybridization.Histological examination was done as well.Results: The concentration of NO-2/NO-3 and the iNOS activity in liver and the serum level of liver enzymes increased significantly,while the eNOS activity decreased in rats of group 2;ALT and AST both decreased significantly,but eNOS activity did not decrease in group 3;while in group 4,eNOS activity significantly decreased,but ALT and AST increased markedly;The levels of NO-2/NO-3 and iNOS activity were relatively low in rats of both groups 3 and 4;The granules showing positive expression of iNOS mRNA significantly increased in groups 2,3,and 4.No difference of eNOS mRNA expression was seen.Liver damages were observed most serious in group 4,and lighter in group 3.No liver damage was seen in group 1.Conclusion: The high expression of iNOS may be one of the important phathophysiological mechanism in the liver damage caused by obstructive jaundice.

关键词(KeyWords)： 胆汁淤积,肝内;一氧化氮合酶;一氧化氮;RNA
cholestasis,intrahepatic;nitric-oxide synthase;nitric oxide;RNA

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 唐宗怀,胡韵,秦建国
TANG Zonghuai1,HU Yun2,QIN Jianguo3(1.Anhui Provincial Red-cross Tongling Hospital

DOI: 10.19367/j.cnki.1000-2707.2007.02.014

参考文献(References)：

• [1]Tschugguel W,Schneeberger C,Unfried G,et al.Ex-pression of inducible nitric oxide synthase in human breastcancer depends on tumor grade[J].Breast Cancer ResTreat.1999(2):145.
• [2]Rereneau S,Arnould L,Jolimoy G,et al.Nitric oxidesynthase in human breast cancer is associated with tumorgrade,proliferation rate,and expression of progesteronereceptors[J].Lab Invest.1999(10):1215.
• [3]Wink DA,Mitchell JB.Chemical biology of nitric oxide:insights into regulatory,cytotoxic,and cytoprotectivemeachamisms of nitric oxide[J].Free Radi Biol med,1998(25):434-456.
• [4]Stoclet JC,Muller B,Andriantsitohaina R,et al.Over-production of nitric oxide in pathophysiology of blood ves-sels[J].Biochemistry,1998(7):826-832.
• [5]Liu P,Xu B,Hock CE,et al.NO modulates P-selectinand ICAM-1mRNA expression of and hemodynamic alter-ations in hepatic I/R[J].Am J Physiol,1998(275):2191-2198.
• [6]Tevaearai HT,Mueller XM,Tepic S,et al.Nitric oxideadded to the sweep gas infusion reduce local clotting forma-tion in adult blood oxygenators[J].ASAIO J,2000(6):719-772.
• [7]Squadrito GL,Pryor WA.Oxidative chemistry of nitric ox-ide:the roles of superoxide,peroxynitrite,and darbon di-oxide[J].Free Radic Biol Med,1998(25):392-403.
• [8]Kroncke K D,Fehsel K.Nitric oxide:cytotoxicity versuscytoprotection-how,why,when,and where[J].Nitricoxide,1997(1):107.
• [9]Hutcheson IR,Whittle BJR,Boughton-smith NK,et al.Role of nitric oxide in maintaining vascular integrity in en-dotoxin induced acute intestinal damage in the rat[J].BrJ Pharmacol.1990(101):815-820.
• [10]Hartleb M,Michielsen PP,Dxiurkowska-Marek A.Therole of nireic oxide in portal hypertensive systemic andportal vascular pathology[J].Acta Gastroenterol Velg,1997(60):222-232.
• [11]Bories PN,Campollo B,Axaou L,et al.Long-lastingNO overproduction in cirrhotic patients with spontaneousbacterial peritonitis[J].Hepatology,1997(25):1328-1333.
• [12]Sanchez Rodriguez A,Criado M,Roudriguez Lopez AM,et al.Increased nitric oxide synthesis and inducible nitricoxide synthase expression in patients with alcoholic andnon-alcoholic liver cirrhosis[J].Clin Sci,1998(94):637-643.
• [13]Arriero MM,Lopez Farre A,Fryeiro O,et al.Expres-sion of inducible nitric oxide synthase in the liver of bileduct-ligated Wistar rats with modulation by lymphom-ononuclear cells[J].Surgery,2001(3):255-266.
• [14]Yao YM,Lu Y,Liang HP,et al.Influence of selectivedecontamination of the digestive tract on cell-mediatedimmune function and bacteria endotoxin translation inthermally injured rats[J].J Trauma,1997(42):1073-1074.
• [15]Wolff,Lubesikie A.Aminoguanidine is an isoform.se-lective mechanism-based inactivator of nitric oxide syn-thase[J].Arch Biochen Biophys,1995(1):290-301.
• [16]MacNaul K L,Hutchinson N I.Differential expression ofiNOS and cNOS mRNA in human vascular smooth musclecells and endothelial cells under normal and inflammatoryconditions[J].Biochem Biophys Res,1993(196):1330-1334.
• [17]Griscavage JM,Rogers NE,Sherman MP,et al.Induc-ible nitric oxide synthase from a rat alveolar macrophagecell line is inhibited by nitric oxide[J].J Immunol,1993(151):6329-6337.
• [18]Doron Schwartz,Margarida Mendonca,Idit Schwartz,etal.Inhibition of constitutive nitric oxide synthase by nitricoxide generated by inducible NOS after lipopolysaccharideadministration provokes renal dysfunction in rats.J ClinInvest,1997(2):439-448.
• [19]Tazi KA,Barriere E,Moreau R,et al.Relationship be-tween protein kinase C alterations and nitric oxide over-production in cirrhotic rat aortas[J].Liver,2002(2292):178-183.

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