基于以MicroRNA为核心的调控链探讨心肾同源学说在2型CRS发病中的作用研究

Type 2 cardiorenal syndrome is the syndrome, which gradually ocurred renal damage in the processing of chronic heart failure with hemodynamic stable condition. Inflammatory reaction plays an important role in the processing of kidney and heart interactions. TCM holds that heart-kidney yang deficiency syndrome is occurred at the middle-late stage of chronic heart failure, and is the main syndrome feature of cardiorenal syndrome. The author proposes that heart kidney homologous is the pathophysiologic foundation in the processing of functional and material damage of heart and kidney, and colsely related to inflammatory reaction mediated. On genetic basis, microRNA effects protein expression of inflammatory reaction, induces heart and kidney damage, then develops cardiorenal syndrome, and is a key process of regulation. Our previous studies showed that yang deficiency syndrome was significantly associated with cardiorenal syndrome and had similar long-term prognosis. The study intends to detecting inflammatory microRNA, markers of inflammatory reaction, markers and expressions of heart and kidney function and clinical features between patients with cardiorenal syndrome and chronic heart failure, then comparing their differences, analysing their correlation of indexs at different levels, preliminary drawing effect of microRNA regulating chain on type 2 cardiorenal syndrome with heart-kidney yang deficiency syndrome. If the theory could be verified, it will provide theoretical basis for systematically explaining cardiorenal syndrome, exploring targeted therapeutic treatment, method, also could gradually expand theory application scope, futher enrich and develop the basic theroy of TCM.

2型心肾综合征（2型CRS）是在慢性心力衰竭（CHF）发展过程中血流动力学相对稳定状态下逐渐发生肾脏损害，炎性反应为其中心肾交互作用核心环节。中医学认为心肾阳虚是CHF中晚期阶段，是CRS发生的主要证候特征。我们提出在CRS过程中，心肾同源是心肾渐次发生功能和物质损害病理基础，与炎性反应介导具有密切关系。microRNA在遗传基因基础上，调节炎性反应蛋白表达，产生心肾损害，形成CRS，是这个调控过程核心环节。我们前期研究显示阳虚证与CRS有显著相关性和相似远期预后。本研究拟检测CHF与CRS患者炎性相关microRNA、炎性反应标记物、心肾功能标记物水平及临床特征，比较差异性，分析不同层面之间相关性，初步勾勒出以microRNA为核心调控链对2型CRS心肾阳虚发展过程的影响。如果这学说能得到验证，将为系统解释CRS、探索有针对性治则、治法和方药提供理论基础，并拓展其应用，丰富和发展中医理论

2型心肾综合征（CRS）是慢性心力衰竭（CHF）导致的慢性肾损伤，具有高发病率、高死亡率的特点，已经成为国内外研究热点。目前认为2型CRS机制复杂，炎性反应是心肾交互作用的核心环节，而microRNA对炎性反应具有重要调控作用。通过前期随访发现，阳虚是2型CRS的主要证候特征。因此，本课题纳入阳虚型CHF和CRS患者各50例，比较两组患者microRNA、炎性反应标记物、心肾功能指标及临床特征的差异，探究心肾阳虚的微观物质基础，并初步观察加味苓桂术甘汤延缓2型CRS发生的作用。研究结果显示：（1）临床特征方面，CRS组NT-proBNP显著升高（P＜0.001），肾功能指标（eGFR、Scr、BUN和UA）显著升高（P＜0.001）；（2）炎性反应标记物方面，CRS组TNF-α水平明显升高（P=0.004），经加味苓桂术甘汤治疗后，两组IL-1β表达水平较治疗前显著下降（P＜0.001），CHF组TLR4表达水平较治疗前显著下降（P=0.043）；（3）miRNAs表达水平方面，CRS组miR-21-5p、miR-223-3p、miR-146a-5p、miR-155-5p及miR-486-3p的表达量呈现下降趋势，但未显示统计学差异，在以后的研究中将扩大样本量进一步验证表达差异。研究结果已发表和录用核心期刊论文9篇，拟投送SCI论文1篇。研究期间培养已毕业博士研究生1名，硕士研究生3名，在站博士后1名，在读硕士研究生1名。本研究有助于加深对2型CRS发生机制的认识，丰富“心肾同源”理论的科学内涵，为中医临床治疗提供理论基础。