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大鼠异种原位肝移植急性排斥反应中一氧化氮合酶细胞定位的意义 被引量:8

Cellular localization of nitric oxide synthase during acute rejection in golden harmster to rat orthotopic liver xenotransplantation
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摘要 目的 探讨一氧化氮合酶(cNOS,iNOS) 在金黄地鼠至大鼠异种原位肝移植急性排斥反应中的细胞定位及其意义.方法 我们应用金黄地鼠至大鼠异种原位肝移植急性排斥反应及大鼠同基因原位肝移植动物模型,应用NADPH 黄递酶组化染色及免疫组化染色观察移植肝组织NOS 的活性及cNOS,iNOS 的蛋白表达.结果 大鼠异种原位肝移植急性排斥反应时血浆NO 代谢产物NO-x 明显增高,环孢菌素A 可显著抑制NO 的合成. 异种肝移植急性排斥反应时,NADPH_d 组化染色及其兔抗大鼠多克隆抗体iNOS,cNOS 免疫组化染色均呈强阳性表达,但以iNOS表达为主.iNOS 主要在肝细胞、肝窦内皮细胞及Kupffer 细胞等炎性细胞表达,而同基因组及免疫抑制治疗组则不表达.结论 原位肝移植肝细胞NO 产物可随移植肝的免疫状态不同而异,肝细胞NO 很可能具有重要的免疫保护作用,NO 合酶及其代谢产物NO-x 在肝移植急性排斥反应中可具有早期的免疫学监测作用. AIM To investigate the effects and cellular localization of nitric oxide synthase (cNOS, iNOS) during acute rejection in the golden hamster to rat orthotopic liver xeno transplantation (OLTx). METHODS The activity of nitric oxide synthase (NOS) and the expression of inducible and endothelial nitric oxide synthase (iNOS & ecNOS) were detected by NADPH diaphorase histochemical and immunohistochemical staining by using a syngeneic Wistar rat OLT and a golden hamster to rat OLTx model. RESULTS During acute rejection in golden hamster to rat OLTx, systemic levels of the nitric oxide metabolite (NO) were found to increase significantly, in contrast, nitric oxide synthesis was inhibited strikingly by administrating cyclosporine (CsA) to recipients, inducible and endothelial nitric oxide synthase (iNOS and ecNOS) were overexpressed in hepatocytes and portal inflammatory cells by NADPH_diaphorase histochemical and immunohistochemical staining. The grafted livers in group B were found to strongly express levels of iNOS protein in hepatocytes and mononuclear portal infiltrates. In contrast, the grafted livers in ISO and group C with CsA expressed no detectable iNOS. CONCLUSION Hepatocyte_derived nitric oxide production varies according to the immunologic status of the grafted liver, and it may be potential immunologic protective. NADPH_diaphorase histochemical staining for NOS and monitoring the serum NO levels could serve as an early sensitive effective marker of immunological surveillance.
出处 《世界华人消化杂志》 CAS 1999年第10期855-860,共6页 World Chinese Journal of Digestology
关键词 肝移植 排斥反应 一氧化氮合酶 liver transplantation rejection nitric oxide/metabolism nitric oxide synthase rats Wistar golden hamster liver pathology immunohistochemistry NADPH diaphorase
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