一氧化氮合酶在梗阻性黄疸大鼠肝脏中的表达

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Wistar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TBIL、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iNOS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.

The Expression of Nitric Oxide Synthase in the Liver of Rats with Obstructive Jaundice and Its Significance

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.