肾脏不仅是排泄器官，也是重要的代谢器官。新观点认为，下丘脑炎症促使能量代谢的神经-体液调节机制失衡，参与糖尿病发生发展。靶向肾脏水代谢的加压素（AVP）能够调节肝脏脂肪变性。课题组前期研究发现在2型糖尿病肾病（T2DN）中存在下丘脑炎症、肾脏异位脂肪沉积与AVP水平升高呈正相关，提示AVP也可能调控肾脏脂质代谢。MCPIP1是炎症因子的负调控子。因此，本项目拟建立T2DN、AVP及受体基因敲除等大鼠模型，构建胶质细胞和神经元共培养系统，探讨由下丘脑炎症上调的AVP通过与其受体结合诱导AMPK/SREBP-1c在肾脏脂肪沉积中的作用及中枢输注MCPIP1的干预效果。本项目从神经-体液调控肾脏代谢的新角度，为防止T2DM向DKD发展，阻止其向ESRD进展提供强有力的宏观理论依据。

Kidney is not only a excretory organ, but also an important metabolic organ.The new viewpoint holds that hypothalamic inflammation leads to the imbalance of neural-humoral regulation of energy metabolism and is involved in the occurrence and development of diabetes.Vasopressin (AVP), which targets renal water metabolism, has been found to regulate hepatic steatosis.Our previous studies found that the presence of hypothalamic inflammation and renal ectopic fat deposition in type 2 diabetic nephropathy (T2DN) was positively correlated with the increased level of AVP, suggesting that AVP may also regulate renal lipid metabolism. MCPIP1 is a negative regulator of inflammatory cytokines.Therefore, rat models such as T2DN, AVP-/-, AVP receptor 1a-/- and microglial-neuron co-culture system will be used to explore the mechanism of AVP regulated by hypothalamic inflammation binding with V1aR on renal fat deposition via AMPK/SREBP-1c and central anti-inflammation effect of MCPIP1 intervention. From a new perspective of neuro-humoral regulation of kidney metabolism, this project provides a powerful macro-theoretical basis for preventing the development of T2DM to DKD and preventing its progression to ESRD.