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

Mechanism of Renal Injury Induced by Metabolic Factors and Prevention of the Injury by Vasoprotective Factors.

代谢因素诱发肾损伤的机制及血管保护因素预防肾损伤。

基本信息

批准号：
14571044
负责人：
SUGA Shinichi
金额：
$ 2.24万
依托单位：
National Cardiovascular Center Research Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

■Hypokalemic Nephropathy(1)We demonstrated an up-regulation of endothelin (ET)-1 production in the cortex and medulla, and an increase in the expression of the ET type A receptor (ETA) and type B receptor (ETB) in the medulla of rats with hypokalemic nephropathy. ETA blockade ameliorated renal tubulointerstitial injury and renal function in hypokalemic nephropathy. ETA blockade ameliorated renal ET-1 production. By contrast, ETB blockade suppressed renal ET-1 production and ETA expression as well as improved renal tubulointerstitial injury and renal ET-1 production and ETA expression as well as improved renal tubulointerstitial injury and renal function in hypokalemic nephropathy. These results suggested that ET-1 can induce renal injury not only via direct activation of ETA, but also by stimulating local production of ET-1 via ETB.(2)We also demonstrated that angiotensin II antagonism ameliorates tubulointerstitial injury and renal function in hypokalemic nephropathy, and suggested that renal angiotensin II generation may contribute to the pathogenesis of hypokalemic tubulointerstitial injury.■Renoprotection by Vasoactive Factors : Adrenomedullin, a potent vasorelaxing peptide and a prosurvival factor for vascular cells, ameliorates tubular necrosis and apoptosis in ischemic reperfusion injury of the kidney possibly by suppressing renal production of TNF-α and interleukin-6.■Searching New Candidate Genes for Diabetic Nephropathy : We found an alteration in the expression of genes related to kidney development and podocyte structure as well as glucose and lipid metabolism and oxidative stress in db/db mice, a model of type 2 diabetes, when compared to the control. This alteration might be related to pathogenesis of early diabetic glomerulopathy.

低钾性肾病（1）我们证实了在低钾性肾病大鼠的皮质和髓质中内皮素（ET）-1的产生上调，以及在髓质中ET A型受体（ETA）和B型受体（ET B）的表达增加。ETA阻断剂可改善低钾肾病肾小管间质损伤和肾功能。ETA阻断可改善肾脏ET-1的产生。与此相反，ETB阻断抑制肾ET-1的产生和ETA的表达，以及改善肾小管间质损伤和肾ET-1的产生和ETA的表达，以及改善肾小管间质损伤和肾功能在低钾性肾病。结果提示，ET-1不仅通过直接激活ETA，而且通过ETB刺激局部ET-1的产生而引起肾损伤。(2)We还证明血管紧张素II拮抗剂改善低钾血症性肾病中的肾小管间质损伤和肾功能，并表明肾血管紧张素II的产生可能有助于低钾血症性肾小管间质损伤的发病机制。肾上腺髓质素，一种有效的血管舒张肽和血管细胞的促存活因子，可能通过抑制TNF-α和白细胞介素-6的肾脏产生来改善肾脏缺血再灌注损伤中的肾小管坏死和细胞凋亡。■寻找糖尿病肾病的新候选基因：我们发现，与对照组相比，db/db小鼠（2型糖尿病模型）中与肾脏发育和足细胞结构以及葡萄糖和脂质代谢和氧化应激相关的基因表达发生了变化。这种改变可能与早期糖尿病肾小球病变的发病机制有关。