Yanagisawa H, Nodera M, Wada O
Department of Hygiene & Preventive Medicine, Faculty of Medicine, Saitama Medical School, Japan.
Ind Health. 1998 Oct;36(4):324-30. doi: 10.2486/indhealth.36.324.
To examine the mechanisms involved in the progression of mercury chloride (HgCl2)-induced acute tubular necrosis (ATN), we investigated the histopathological changes and the expression of inducible nitric oxide synthase (iNOS) mRNA and protein in renal cortices of rats at 20 hours after exposure to HgCl2. The expression of iNOS mRNA was significantly augmented in renal cortices of rats with HgCl2-induced acute renal failure (ARF). Likewise, the induction of iNOS protein was observed in damaged proximal tubule epithelial cells of rats with HgCl2-induced ARF. Pretreatment of rats with iNOS inhibitor aminoguanidine, however, suppressed the development of proximal tubule epithelial cell injury and prevented an increase in blood urea nitrogen and serum creatinine as well as resulting in a marked fall in iNOS mRNA and protein in rats with HgCl2-induced ARF. These observations indicate that the induction of iNOS may play a role in the progression of HgCl2-induced ATN through the exacerbation of proximal tubule epithelial cell damage.
为了研究氯化汞（HgCl2）诱导的急性肾小管坏死（ATN）进展过程中的相关机制，我们在大鼠暴露于HgCl2后20小时，研究了其肾皮质的组织病理学变化以及诱导型一氧化氮合酶（iNOS）mRNA和蛋白的表达。在HgCl2诱导的急性肾衰竭（ARF）大鼠的肾皮质中，iNOS mRNA的表达显著增加。同样，在HgCl2诱导的ARF大鼠受损的近端小管上皮细胞中观察到了iNOS蛋白的诱导。然而，用iNOS抑制剂氨基胍预处理大鼠，可抑制近端小管上皮细胞损伤的发展，并防止血尿素氮和血清肌酐升高，同时导致HgCl2诱导的ARF大鼠的iNOS mRNA和蛋白显著下降。这些观察结果表明，iNOS的诱导可能通过加剧近端小管上皮细胞损伤，在HgCl2诱导的ATN进展中发挥作用。
