消融颈动脉体（CB）降低交感活性是治疗慢性心力衰竭（CHF）的重要探索方向。但毁损CB存在不可控、创伤大、损害呼吸调节功能等缺陷。P2X3是CB信号传导的关键受体，同时在全身组织广泛分布，静脉使用该受体阻断剂可剂量依赖性降低CB和交感活性，但选择性差。项目拟利用CRISPR/Cas9技术构建P2X3基因敲除质粒，并将其与靶向阳离子脂质微泡整合，构建出物理性能良好、造影效果与寻靶能力俱佳的载P2X3敲除质粒靶向超声微泡（PTMB）。项目还将验证在低强度聚焦超声介导下PTMB的体内转染效率及其剂量与CB P2X3受体表达水平之间的量-效关系。最终通过调控PTMB的剂量，靶向、定量下调CB P2X3受体的表达，控制性调节CB和交感活性，改善CHF的心功能异常、心室重构和预后，为实现CHF安全、高效、可控的CB调节治疗提供理论和实验基础，为优化CHF的治疗策略提供新手段。

Denervating carotid body (CB) to decrease the activity of sympathetic nervous system (SNS) is investigating for the treatment of chronic heart failure (CHF). However, destroyed CB by surgical resection or ablation has several limitations including uncontrollability, traumatic and respiratory function disturbance. P2X3 receptor, widely spread in human tissues, plays a key role in the signal transmission of CB and intravenously using its antagonists could dose-dependently decrease the CB and SNS activity, but lack of selectivity. We aimed to construct the P2X3 gene knock-out plasmid by CRISPR-Cas9 system and combine it with targeted cationic lipid microbubble to produce a P2X3 knock-out plasmid targeted microbubble (PTMB) with excellent physical properties and favorable imaging and targeting effects. Our study would further investigate the transfection efficiency in vivo and the relationship between the dosage of PTMB and the expression of CB P2X3 receptor. Finally, we intended to regulate the dosage of PTMB to quantitatively downregulate the expression of CB P2X3 receptor, controlled decrease the activity of CB and SNS, and improve the cardiac dysfunction, cardiac remodeling and prognosis of CHF. This study will provide theoretical and experimental foundations for performing safety, efficient and controllable CB modulation therapy and also optimize the clinical strategy for CHF patients.