权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Elucidation of the new role of nitric oxide in the cortical collecting duct that regulates and acid base balance

阐明一氧化氮在皮质集合管中调节酸碱平衡的新作用

基本信息

批准号：
18591206
负责人：
WATANABE Seiji
金额：
$ 2.26万
依托单位：
University of Occupational and Environmental Health, Japan
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

The cortical collecting duct (COD) of the kidney plays an important role in acid base homeostasis and is comprised of principal cells and intercalated cells. The CCD contains two types of intercalated cells: A-intercalated cells secrete H and B-intercalated cells secrete HCO3 (-). On the other hand, Nitric oxide (NO) is produced in almost all tissues and organs, exerting multiple biological actions under both physiological and pathological conditions. NO is synthesized by three different isoforms of NO synthase (NOS): neuronal, inducible, and endothelial NOSs. The CCD is known to express each isoform and NO has important actions in the CCD. But less is known about how NO affects the maintenance of acid-base homeostasis in the CCD. At first, we examined whether NO production was required for adaptation of the COD to metabolic acidosis or alkalosis. We incubated the dissected CCD from normal mouse kidney and loaded it with NO-sensitive fluorescent dyes, diaminofluoresceins (DAF). We measured its fluorescence in the CCD after changing acid or alkali incubation solution. Only When it changed into low pH, NO was produced immediately at, the some cells and spread in the CCD. After these experiments, to identify which cells produce NO, we tried to label the same CCD with either AE1 (the marker of Principal cells), PNA (the marker of 6 cells), or band 3 (the marker for a cells). But we were not able to identify the cells. Next, we used each single NOS knockout and triple NOS knockout mice to investigate the role of NO in regulating the acid-base balance in the CCD. We have reported that triple NOS knockout mice cause nephrogenic diabetes insipidus at the late stage after birth, and that renal tubular apoptosis in the CCD is involved in the pathogenesis of nephrogenic diabetes insipidus. Therefore we need the CCD at the early stage after birth. We are planning to experiment using it.

肾脏皮质集合管(COD)在维持酸碱平衡中起着重要作用，它由主细胞和夹层细胞组成。该细胞含有两种类型的嵌合细胞：A-嵌合细胞分泌H，B-嵌合细胞分泌HCO3(-)。另一方面，一氧化氮(NO)在几乎所有的组织和器官中产生，在生理和病理条件下都发挥着多种生物学作用。NO由神经元型、诱导型和内皮型三种不同亚型的一氧化氮合酶(NOS)合成。已知的是，ccd表达每一种亚型，而NO在ccd中具有重要作用。但关于NO如何影响细胞内酸碱平衡的维持，我们知之甚少。首先，我们检查了COD是否不需要产生以适应代谢性酸中毒或碱中毒。我们从正常小鼠肾组织中分离出细胞，并用不敏感的荧光染料二氨基荧光素(DAF)对其进行负载。更换酸碱孵育液后，测量其在电荷耦合器件中的荧光。只有当它变成低pH时，NO才会在某些细胞上立即产生并扩散到CCD中。在这些实验后，为了确定哪些细胞产生NO，我们试图用AE1(主细胞的标记)、PNA(6个细胞的标记)或Band 3(细胞的标记)来标记相同的Cd。但我们无法识别这些细胞。接下来，我们使用每个单独的NOS基因敲除小鼠和三个NOS基因敲除小鼠来研究NO在调节CCD中的酸碱平衡中的作用。我们曾报道，三重一氧化氮合酶基因敲除小鼠在出生后的晚期可引起肾源性尿崩症，而小鼠肾小管上皮细胞的凋亡参与了肾源性尿崩症的发病机制。因此，我们需要在出生后的早期阶段进行检查。我们正计划用它进行试验。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Schwartz, Akha Shirahata, Akio Fujimura Endothelin and nitric oxide mediate adaptation of the cortical collecting duct to metabolic acidosis

Schwartz、Akha Shirahata、Akio Fujimura 内皮素和一氧化氮介导皮质集合管对代谢性酸中毒的适应

DOI：
发表时间：
2006
期刊：
影响因子：
0
作者：
Shuichi Tsuruoka;Seiji Watanabe;George J
通讯作者：
George J

Accelerated renal lesion formation after unilateral ureteral obstruction in inice lacking all nitric oxide synthase isoforms : Involvement of the renin-aligiotensin system

缺乏所有一氧化氮合酶亚型的小鼠单侧输尿管梗阻后加速肾脏病变形成：肾素-阿利血管紧张素系统的参与

DOI：
发表时间：
2008
期刊：
影响因子：
0
作者：
Morisada N;Tsutsui M;Nomura M;Sabanai K;Tanimoto A;Watanabe S;Nishii H;Matumoto T;Sasaguri Y;Shimokawa H;Yanagihara N;Shirahata A
通讯作者：
Shirahata A

Endothelin and nitric oxide mediate adaptation of the cortical collecting duct to metabolic acidosis

内皮素和一氧化氮介导皮质集合管对代谢性酸中毒的适应

DOI：
发表时间：
2006
期刊：
Am J Physiol Renal Physiol 291
影响因子：
0
作者：
Shuichi Tsuruoka;Seiji Watanabe;Jeffrey M.Purkerson;Akio Fujimura;and George J.Schwartz
通讯作者：
and George J.Schwartz

NO合成酵素完全欠損マウスに見られた一側尿管結紮後の高度腎組織障害:レニン・アンジオテンシン系の関与

在完全缺乏 NO 合酶的小鼠中观察到单侧输尿管结扎后严重的肾组织损伤：肾素-血管紧张素系统的参与