基于多组织仿生构筑研究AVP/RAAS轴对心肌重构和肾组织纤维化的双重调控机制

心肌重构引发的心力衰竭是心肾综合征患者死亡的常见病因。微环境血供状况是心肌重构的重要影响因素，我们前期发现导电微环境能诱导新生血管形成，减缓心衰的发生，而其具体作用机制仍不明确。心梗后急剧分泌的血管加压素（AVP）能引起冠状动脉微血管持续收缩，导致心肌缺血性损伤；过量的AVP也引起肾损伤，并与RAAS密切相关。我们推测，机体内可能存在一个AVP/RAAS轴，能同时调控新生血管形成、心肌重构和肾脏纤维化。本课题拟利用生物反应器和WT1阳性细胞进行多组织仿生构筑，建立“管道心肌组织-智能管道心肌组织”以及“管道心肌组织-管道肾组织”的3D共培养体系，研究AVP/RAAS轴在微脉管系统形成、心肌重构以及肾组织纤维化中的调控作用。此外，采用高敏感度的光纤生物传感器实现AVP与RAAS成分的实时检测。据此，进一步构建干预微环境AVP水平的功能性导电心肌补片，探讨其对心肾综合征大鼠心肌损伤的保护作用。

Heart failure caused by cardiac remodeling is a common cause of death in patients with cardiorenal syndrome. Microenvironment blood supply is an important factor affecting cardiac remodeling. We have found that the conductive microenvironment can induce angiogenesis and slow down the occurrence of heart failure, but its further mechanism is still unclear. The rapid secretion of vasopressin (AVP) after myocardial infarction can cause continuous contraction of coronary microvessels, resulting in ischemic myocardial injury. Excessive AVP is also closely related to RAAS and renal dysfunction. We speculate that there may be an AVP/RAAS axis in the body that regulates neovascularization, myocardial remodeling, and renal fibrosis. Based on the characteristics of bioreactor and the WT1 positive cells, we intend to establish a 3D co-culture system including "conduit cardiac tissue coculturing with intelligent conduit cardiac tissue" and "conduit cardiac tissue co-culturing with conduit kidney tissue". Therefore, we will explore the influence of the AVP/RAAS axis on the formation of microvascular system, myocardial remodeling and renal fibrosis. In addition, a high sensitivity optical fiber biosensor will be used to detect the AVP and RAAS components in real-time. Accordingly, a functional conductive myocardial patch intervening the microenvironment AVP levels was further constructed to investigate its protective effect on myocardial injury in rats with cardiorenal syndrome.