干预主动脉肾神经节治疗心梗性心衰及与外泌体关联性研究

Previous studies have demonstrated that renal denervation (RD) can slow down and even reverse the progress of heart failure. Whereas the precision of RD can hardly be guaranteed and the problem caused by nerve regeneration still exists. ARG is the dominating ganglion innervating the renal sympathetic nervous which elevate the blood pressure more effectively than renal sympathetic nervous when receiving electronic stimulation. Our study has demonstrated the effectiveness of ARG damage to block the renal sympathetic nervous. Moreover, we have found out that the serum level of some kinds of renal-originating miRNA exosomes which can regulate cardiovascular system changed significantly after RD therapy. Thus, in the present study, we will compare the effectivity and security of RD and ARG damage therapy by long-term monitor of electrocardiography and blood pressure, nerve signal analysis, neure staining, biochemistry and immunology detection, echocardiography and so on. We hope to evaluate the feasibility of ARG as a novel target to treat heart failure. Meanwhile, we will demonstrate the change of miRNA exosomes in renal, serum and urine to evaluate its significance as an efficacy indicator in the treatment of heart failure and as a potential target for intervention. This study will find the more exact intervention target and humoral regulation mechanisms of RD and explore the specific indicators to monitor therapy efficacy.

研究显示，去肾交感神经（RD）可以延缓或逆转心衰进展。RD的精准性和神经再生是影响疗效的关键。主动脉肾神经节（ARG）是支配肾交感神经的主要神经节。我们的前期研究发现，精准干预ARG阻断肾交感神经效果更显著；同时我们发现，肾脏来源具有心血管调节作用的外泌体miRNA，在心衰动物变化显著。为证实ARG是比RD治疗心梗性心衰更好的靶点，并研究外泌体miRNA作为疗效监测指标的可能，本研究将利用犬心梗性心衰模型，通过心电血压遥测、神经信号分析、神经染色、生化免疫检测、心脏超声等，对比精准干预ARG和RD疗效及神经再生的差异，观察ARG部分损毁后的副作用，评估ARG作为新靶点的可能；同时通过RT-PCR等分子生物学技术，对比治疗前后肾组织、血清、尿液中外泌体miRNA的变化，进一步阐明疗效机制，探索作为疗效监测指标的可能。本研究将为ARG成为心衰治疗新靶点和外泌体miRNA作为疗效的监测指标提供依据。

研究显示，去肾交感神经（RD）可以延缓或逆转心衰进展。RD的精准性和神经再生是影响疗效的关键。主动脉肾神经节（ARG）是支配肾交感神经的主要神经节。我们的前期研究发现，精准干预ARG阻断肾交感神经效果更显著；同时我们发现，肾脏来源具有心血管调节作用的外泌体miRNA，在心衰动物变化显著。为证实ARG是比RD治疗心梗性心衰更好的靶点，并研究外泌体miRNA作为疗效监测指标的可能，本研究将利用犬心梗性心衰模型，通过心电血压遥测、神经信号分析、神经染色、生化免疫检测、心超等，对比精准干预ARG和RD疗效及神经再生的差异，观察ARG部分损毁后的副作用，评估ARG作为新靶点的可能；同时通过RT-PCR等分子生物学技术，对比治疗前后肾组织、血清、尿液中外泌体miRNA的变化，进一步阐明疗效机制，探索作为疗效监测指标的可能。. 本研究首先验证了主动脉肾神经节解剖定位及其与肾神经的解剖关系，然后构建急性心肌梗死后心衰犬模型，进行主动脉肾神经节消融，通过肾动脉周围神经HE、Masson、TH染色，验证了主动脉肾神经节消融能够使肾交感神经破坏。继而分析模型犬的心超、血浆肾素、血管紧张素II、醛固酮、去甲肾上腺素水平，发现主动脉肾神经节消融治疗能够改善急性心肌梗死后心衰犬模型的心功能，能够抑制其RAAS及交感神经系统的活性。通过分析循环外泌体及肾组织miRNA，发现miRNA-21、miRNA-199a、miRNA-200a可能参与ARG治疗心梗后心衰的机制，本研究将为ARG成为心衰治疗新靶点和外泌体miRNA作为疗效的监测指标提供依据。