PROJECT 4

肾脏在长期控制动脉压中起主要作用[159-161]。因此，任何试图模拟高血压对心血管系统的原因和影响的尝试都需要考虑肾功能。本项目将开发两个连接的肾功能模型（图2.11）。生理学模型将模拟血流、运输和上皮细胞代谢;基因水平的分子模型将模拟转录、信号传导和生化机制，这些机制与单个肾单位段（髓质粗升支（mTAL））中的超氧化物特异性相关。这两种模型将通过对骨髓血流的调节来整合。将生理建模与途径特异性分子建模相结合的创新方法有望在几种大鼠模型中产生关于基因-疾病关系的新假设。

The kidney plays a primary role in the long term control of arterial pressure [159-161]. Thus any attempt at modeling the causes and effects of hypertension on cardiovascular system will require accounting for renal function. This project will develop two connected models (Figure 2.11) of renal function. A physiological model will simulate blood flow, transport, and epithelial cell metabolism; a gene-level, molecular model will simulate transcriptional, signaling, and biochemical mechanisms related specifically to superoxide in a single nephron segment, the medullary thick ascending limb (mTAL). The two models will be integrated through the regulation of medullary blood flow. The innovative approach of integrating physiological modeling with pathway-specific molecular modeling is expected to generate novel hypotheses regarding gene-disease relationships in several rat models.