Nakamura S
Department of Pediatrics, Kitasato University School of Medicine, Kanagawa, Japan.
Nihon Jinzo Gakkai Shi. 1997 Jul;39(5):447-54.
Nitric oxide (NO) is an important factor in tissue trauma, but its detailed role in the pathogenesis remains unknown. In autoimmune vasculitis, it is possible that NO in one of the factors underlying tissue trauma and induction of autoimmune antibodies. To study its role on an animal model using mercury chloride (HgCl2), Brown Norway rats (BN rats) were given five injections of] HgCl2, each 1 mg/kg, over 10 days. Vasculitis and production of some autoimmune antibodies developed after HgCl2 injections. Urine nitrate/nitrite, metabolic production of NO, was produced in advance of the production of other autoimmune antibodies. To elucidate the role of NO, NG-nitro-L-arginine methyl ester (L-NAME), which is a nitric oxide synthase (NOS) inhibitor, was given in addition to HgCl2, at the daily dose of 30 mg/kg. There was no difference in production of autoimmune antibodies between this group and the control group, but urine protein excretion was suppressed in the HgCl2 + L-NAME group (p < 0.001). By immunohistochemical study, inducible NOS was positive in small vessels and mesangial cells in rat kidney. We conclude that in this animal model, over-production of NO leads to the production of autoimmune antibodies and inhibition of NOS production ameliorates proteinuria. These results suggest that NO plays an important role in the induction of renal injury in the rat model of autoimmune vasculitis.
一氧化氮（NO）是组织创伤中的一个重要因素，但其在发病机制中的具体作用尚不清楚。在自身免疫性血管炎中，NO可能是组织创伤和自身抗体诱导的潜在因素之一。为了在使用氯化汞（HgCl2）的动物模型中研究其作用，给棕色挪威大鼠（BN大鼠）在10天内注射5次HgCl2，每次1mg/kg。注射HgCl2后出现了血管炎和一些自身抗体的产生。尿硝酸盐/亚硝酸盐，即NO的代谢产物，在其他自身抗体产生之前就已出现。为了阐明NO的作用，除了HgCl2外，还给予了一氧化氮合酶（NOS）抑制剂NG-硝基-L-精氨酸甲酯（L-NAME），每日剂量为30mg/kg。该组与对照组之间自身抗体的产生没有差异，但HgCl2 + L-NAME组的尿蛋白排泄受到抑制（p < 0.001）。通过免疫组织化学研究，诱导型NOS在大鼠肾脏的小血管和系膜细胞中呈阳性。我们得出结论，在这个动物模型中，NO的过度产生导致自身抗体的产生，而抑制NOS的产生可改善蛋白尿。这些结果表明，NO在自身免疫性血管炎大鼠模型的肾损伤诱导中起重要作用。
