Pathophysiological analysis for tissue renin-angiotensin-system using Cre-loxP system

条件性血管紧张素原基因敲除小鼠被用于产生血管紧张素原基因。组织肾素-血管紧张素系统的病理生理学分析我们利用ATG-/-小鼠研究了肾素-血管紧张素系统(RAS)在改变饮食盐摄入量过程中对致密斑环氧合酶-2(COX-2)的调节作用。这项研究表明，致密斑内COX-2活性可以通过独立于RAS的机制被盐摄入调节，并且COX-2的表达在功能上与ATG-/-小鼠的肾皮质N-NOS活性有关(Nephron Physiol.2006)。在血管紧张素-1a受体基因敲除(AT1a-/-)小鼠和ATG-/-小鼠中，研究了饮食盐摄入量改变对肾内皮细胞一氧化氮合酶(ENOS)表达的影响。本研究证实了AT1a受体介导的信息输入在维持肾血管eNOS表达和活性方面起着关键作用，尤其是在盐水平衡和全身血压变化中(J Am Soc Nephrol，2004，Cell Organization RES，2006)。我们研究了AT1受体相关蛋白在肾单位节段的分布(Kidney Int，2006)。我们利用ATG-/-评估血管紧张素II在免疫介导性结肠炎发病机制中的作用。这项研究表明RAS参与了结肠的免疫系统(Gut，2005)。这些结果表明，拮抗RAS是治疗组织损伤的一种潜在的预防性策略。

Generation of loxP-franked (floxed) angiotensinogen mice.The conditional angiotensinogen knockout construct was used to generate floxed angiotensinogen mice. Heterozygous mice were bred to generate homozygous mice.Pathophysiological analysis of tissue renin-angiotensin-systemWe examined the role of the renin-angiotensin system (RAS) in the regulation of macula densa cyclooxygenase-2 (COX-2) during altered dietary salt intake using Atg-/- mice. This study demonstrated that COX-2 activity in the macula densa can be regulated by salt intake through a mechanism independent of the RAS, and COX-2 expression is functionally linked to renal cortical N-NOS activity in Atg-/- mice (Nephron Physiol.2006).The effects of altered dietary salt intake on renal endothelial nitric oxide synthase (eNOS) expression were determined in angiotensin type-1a receptor gene knockout (AT1a-/-) mice and Atg-/- mice. This study demonstrated that AT1a receptor-mediated inputs play critical roles in maintaining renal vascular eNOS expression and activity during changes in salt-water balance and systemic BP (J Am Soc Nephrol, 2004, Cell Tissue Res, 2006).We examined the distribution of AT1 receptor-associated protein in nephron segments (Kidney Int,2006).We evaluated the effect of angiotensin II on the pathogenesis of immune mediated colitis using Atg-/-. This study revealed that RAS is involved in the immune system in the colon (Gut,2005).These results demonstrated that an antagonism of the RAS is a potential prophylactic strategy for the treatment of tissue damage.