基于shRNA靶向沉默P2X3受体探讨推桥弓干预DOCA小型猪的降压机制

高血压是多种心脑血管疾病的重要病因。颈动脉体的活性增加会导致交感神经响应异常升高，从而引起血压升高，在高血压患者和动物模型中，P2X3受体在颈动脉体中表达水平是血压正常者的5倍，使用P2X3受体拮抗剂后，颈动脉体的兴奋程度降低，交感神经系统活性下降，血压随之下降，因此，能够抑制P2X3受体的表达就能控制血压。推桥弓是防治高血压的核心手法，桥弓穴定位与颈动脉体吻合，课题组前期研究证实推桥弓治疗高血压疗效确切，在相应脑区有特异性反应，且证实推桥弓降压机制并非单纯刺激压力感受器。因此我们提出假说，推桥弓是通过刺激颈动脉体，使颈动脉体内P2X3受体表达受抑制，从而降低颈动脉体活性，使交感神经传出冲动减少，进而控制血压。本课题拟以DOCA小型猪高血压模型为载体，采用shRNA靶向沉默颈动脉体中P2X3受体，从P2X3受体在“颈动脉体活性-交感神经响应”中的介导机制入手，科学阐述推桥弓降压的分子机制。

Hypertension is an important cause and primary risk factor of cerebrovascular diseases. The increased activity of the carotid body will lead to an abnormal increase in sympathetic response, which will lead to an increase in blood pressure. Therefore, by reducing the excitability of the carotid body, blood pressure can be controlled. In patients with high blood pressure and hypertension animal models,P2X3 receptor expression levels in carotid body is five times, when using P2X3 receptor antagonist, the excitation of carotid body is reduced, the sympathetic nervous system activity decreased,blood pressure decreased significantly, therefore, can inhibit P2X3 receptor expression can effectively control the blood pressure. Pushing Qiaogong acupoint is the core massage technique for the prevention and treatment of hypertension,and the anatomical location of Qiaogong acupoint is consistent with the carotid body.The previous study of the research group has confirmed that the Qiaogong acupoint is effective in the treatment of hypertension,and there is a specific response in the corresponding brain areas, and it has been confirmed that the hypotensive mechanism of Pushing Qiaogong acupoint is not just to stimulate the pressure receptor.Therefore,we put forward the hypothesis that pushing Qiaogong acupoint is to inhibit the expression of P2X3 receptor in the carotid artery by stimulating the carotid body, so as to reduce the activity of the carotid body and reduce the sympathetic efferent impulse, so as to effectively control blood pressure.This project intends to take DOCA miniature pig model of hypertension as the carrier, and use shRNA to target and silence P2X3 receptor in carotid body.Starting from the mediating mechanism of P2X3 receptor in "carotid body activity - sympathetic response", this study compares and studies the principle of pushing Qiaogong acupoint to reduce blood pressure, and scientifically expounds the molecular mechanism of pushing Qiaogong acupoint to reduce blood pressure.