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Molecular preventive medicine on floching the onset and progression of enviromental Paramgul metals, pertisclarly mercay indiuced topicity

环境副金属金属的发病和进展的分子预防医学，特别是怜悯引起的话题

基本信息

批准号：
12670327
负责人：
YANAGISAWA Ihroyuki
金额：
$ 2.11万
依托单位：
Saitama Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670327/
关键词：
HgCl_2 acute renal failure endothelin nitric oxide nitric oxide synthrse 一酸化窒素分化酵素

项目摘要

The present study was designed to elucidate the mechanisms responsible for the progression of HgC1_2-indnced acute renal failure(ARF). At the glomerulur level, there was endothelin(ET)-1 expression in glomerular mesangial cells, glomlar epithelial cells and juxtaglomernlar cells. However, the expression of endothelial type(e) nitric oxide synthase(NOS) and brain type(b) NOS was observed in glomerular endothelial cells and juxtaglomerular cells and in glomerular epithelial cells and macula densa cells, respectively. ET-1 expression was significantly increased in the HgCl_2-induced ARF model when compared to the control model. Inversely, the expression of eNOS and bNOS was significantly decreased in the HgCl_2-induced ARF model relative to the control model. It is known that ET-1 is a potent vasoconstrictor. Also, it is reported that nitric oxide(NO) derived from eNOS and bNOS is a vasodilator. An increase in ET-1 and a decrease in NO lead to a fall in glomerular filtration rate through a decrement in the ultrafiltration coefficient(Kf) due to glomerular mesangial and epithelial cell contraction and via a decrement in glomerular capillary plasma floW(Q_A) due to an increment in afferent alteriole resistance. Thus, it is suggested that the vasoconstrictor, ET-1 and the vasodilator NO play a crucial role in the progression of HgCl_2-induced ARF through a fall in Kf and Q_A. In addition, prior administration of the angiotensin receptor type 1 antagonist, TCV-116 inhibited ET-1 expression in the HgCl_2-induced ARF model, indicating that angiotensin II may be involved in the regulation of ET-1 expression

本研究旨在阐明HgCl2诱导的急性肾功能衰竭(ARF)的发病机制。在肾小球水平，肾小球系膜细胞、肾小球上皮细胞和肾小球旁细胞均有ET-1的表达。内皮型(E)一氧化氮合酶(NOS)和脑型(B)NOS分别在肾小球内皮细胞、肾小球旁细胞、肾小球上皮细胞和致密黄斑细胞中表达。与对照组相比，HgCl2诱导的ARF模型中ET-1的表达显著增加。相反，HgCl2诱导的ARF模型中eNOS和bNOS的表达明显低于对照组。已知ET-1是一种强有力的血管收缩因子。另据报道，内皮型一氧化氮合酶和内皮型一氧化氮合酶产生的一氧化氮(NO)是一种血管扩张剂。ET-1的升高和NO的降低导致肾小球滤过率下降，其机制是肾小球系膜细胞和上皮细胞收缩引起的超滤系数(KF)减少，以及肾小球传入动脉阻力增加导致肾小球毛细血管血浆流量(Q_A)减少。提示血管收缩因子ET-1和血管扩张剂NO通过降低KF和Q_A在HgCl2诱导的ARF中起重要作用。此外，在HgCl2诱导的ARF模型中，血管紧张素受体1型拮抗剂TCV-116抑制了ET-1的表达，提示血管紧张素II可能参与了ET-1的表达调节。