盐敏感是慢性肾脏病（CKD）常见的病理生理改变。增加盐摄入除增高血压外，还促进肾纤维化进展、胰岛素抵抗和内皮功能障碍，然其机制尚未阐明。我们前期工作证实，高盐摄入通过脑和肾脏局部肾素血管紧张素系统（RAS）的相互作用促进肾脏炎症和纤维化，故我们假设：CKD时肾单位丧失和盐负荷能通过交感传入和传出反射弧活化中枢-外周组织RAS轴，通过病理正反馈环促进组织氧化应激，导致脂肪组织胰岛素抵抗和微血管功能障碍等靶器官损伤。为验证该假说，本项目拟通过CKD动物模型，进一步研究盐负荷对脂肪组织和微血管功能障碍的作用，揭示中枢-外周组织RAS轴活化在上述靶器官损伤发病学中的作用及其调节机制。鉴于胰岛素抵抗和微血管功能障碍与CKD的心血管预后密切相关，该研究将揭示CKD时盐敏感状态的机制，为防治CKD心血管病变提供新理念。

In addition to increasing blood pressure, salt excess promotes renal fibrosis, insulin resistance and endothelial dysfunction in chronic kidney disease (CKD) by uncertain mechanisms. Our recent study demonstrates that salt contributes to progression of renal fibrosis through a neuronal interaction between brain and renal RAS. Therefore, we hypothesize that cerebral-peripheral RAS axis is interlinked by a sympathetic reflex that is activated by salt in setting of CKD. This pathophysiological feedback circle contributes to target organ damage such as insulin resistance in adipose tissue and microvascular dysfunction. The proposed study will investigate the effects of salt excess on adipose tissue perturbation and microvascular dysfunction in a model of CKD and investigate the role of cerebral-peripheral RAS axes in the pathogenesis of these adverse endpoints. Given that insulin resistance and microvascular dysfunction are common in CKD and closely associated with the cardiovascular outcomes in these patients, the study will identify novel regulatory mechanisms underlying these conditions in response to salt load, and thereby provides insights into potential new strategies for prevention and management not only of hypertension, but also of the other important cardiovascular risk factors in CKD.