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摘要: 针对高血压这一主要心血管病危险因素进行有效防治，可以降低心血管病死亡风险。然而，中国高血压的知晓率、治疗率和控制率均处于较低水平，尤其是控制率极低，心血管病防治面临巨大挑战和困境。为进一步探索高血压安全有效的治疗方法，改善治疗依从性，本团队在高血压治疗性疫苗领域多年耕耘，使本研究团队对这一治疗手段的应用前景充满希望。本文将重点介绍高血压生物靶向治疗领域尤其是治疗性疫苗的研究进展，希望以此推动生物靶向治疗高血压领域的基础研究与临床转化。Abstract: Effective prevention and treatment of hypertension reduce the risk of cardiovascular death.However, the rate of awareness, treatment, and control for hypertension in China is still low, prevention and treatment of cardiovascular diseases is facing huge challenges and difficulties.In order to further explore safe and effective therapeutic methods for hypertension and improve treatment compliance, our team has worked hard for long years in the field of therapeutic hypertension vaccine, which makes us full of hope for the application prospects of therapeutic vaccine.This article will systematically introduce the research progress in the field of bio-targeted treatment for hypertension, especially therapeutic hypertension vaccine, aiming to promote basic research and clinical translation in the field.
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Key words:
- hypertension /
- bio-targeted treatment /
- therapeutic vaccine /
- gene targeted therapy
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表 1 生物靶向治疗高血压的药物
Table 1. Drugs of bio-targeted treatment for hypertension
高血压靶点 疫苗形式 血压降低水平 发表年份 肾素 全抗原 在高血压狗和高血压大鼠中观察到降压作用 1958 全抗原 降低狨猴收缩压38 mmHg，但导致肾脏免疫性损害 1987 KLH偶联疫苗 降低自发性高血压大鼠收缩压15 mmHg 2013 AGT 干扰RNA药物(zilebesiran) 24 h动态收缩压降低超过15 mmHg 2020 ASO(IONIS-AGT-LRx) 单药治疗血压平均下降8/1 mmHg，联合用药血压平均下降12/6 mmHg 2021 AngⅠ KLH偶联疫苗(PMD3117) 临床试验未见血压降低 2003 AngⅡ Qβ VLP偶联疫苗(CYT006-Qβ) 降低自发性高血压大鼠血压(收缩压降低21 mmHg)，临床试验大剂量组血压降低9/4 mmHg 2007 KLH偶联疫苗 降低高血压动物血压(具体降幅未知) 2013 HAV载体嵌合疫苗 降低自发性高血压大鼠血压23/12 mmHg 2013 DNA疫苗(AGMG0201) 降低自发性高血压大鼠血压，Ⅰ/Ⅱa期临床试验正在进行中 2015 AT1R TT偶联疫苗 降低自发性高血压大鼠收缩压17 mmHg 2006 KLH偶联疫苗 降低自发性高血压大鼠血压(未指出具体血压降幅) 2012 Qβ VLP偶联疫苗(ATRQβ-001) 降低高血压模型动物收缩压(小鼠降低35 mmHg，大鼠降低19 mmHg) 2013 α1DR Qβ VLP偶联疫苗(ADRQβ-004) 降低自发性高血压大鼠收缩压18 mmHg 2019 L型钙通道/AT1R二价疫苗 HBcAg载体嵌合疫苗 降低高血压动物血压(收缩压降低25 mmHg) 2019 HAV：甲型肝炎病毒；TT：破伤风类毒素；HbcAg：乙肝核心抗原。 
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