基于ACE-AngⅡ-AT1轴及ACE2-Ang(1-7)-Mas轴探讨原发性高血压的中医证候实质

Exploring the Essence of Traditional Chinese Medicine Syndromes Matched with Essential Hypertension through ACE-AngⅡ-AT1 Axis and ACE2-Ang(1-7)-Mas Axis

原发性高血压(EH)是一种由遗传与环境因素共同作用而引起的多基因遗传性疾病。表观遗传学紧密联系环境因素与遗传因素,而环境因素可能通过影响EH相关基因的表观遗传学而造成血压的变化。证候作为机体对内外环境和致病因素做出反应后所处的一种功能状态,与表观遗传学的动态变化规律具有一致性。微小核糖核酸(miRNA)作为表观修饰的方式之一,在不改变脱氧核糖核酸(DNA)序列的情况下,可通过对基因组的修饰改变遗传表型。肾素-血管紧张素系统(RAS)在调节血压方面起关键作用,血管紧张素转换酶-血管紧张素Ⅱ-血管紧张素Ⅱ1型受体(ACE-AngⅡ-AT1)轴是RAS经典代谢途径,血管紧张素转换酶2(ACE2)可水解AngⅡ产生Ang(1-7)通过作用于Mas受体发挥舒张血管等作用,即ACE2-Ang(1-7)-Mas轴。基因表达及其信号传导的相关调控因素可能与不同证候的生物学支配机制密切相关,以ACE-AngⅡ-AT1轴和ACE2-Ang(1-7)-Mas轴及其靶向miRNA与内外环境的交互作用为切入点,有助于从系统生物学角度阐明EH不同证候形成的可能机制,进而揭示EH的中医证候实质。

Essential hypertension(EH) is a polygenic hereditary disease caused by the combined action of genetic and environmental factors. Epigenetics is closely related to environmental factors and genetic factors, and environmental factors may cause changes in blood pressure by affecting the epigenetics of EH-related genes. Traditional Chinese medicine(TCM) syndrome, as a functional state reflecting the body responses to internal and external environments and pathogenic factors, is consistent with the dynamic law of epigenetics. Microribonucleic acid(miRNA) is an apparent modification method, and can change the genetic phenotype by modifying the genome without changing the sequence of deoxyribonucleic acid(DNA). The renin-angiotensin system(RAS) plays an important role in regulating blood pressure, and the angiotensin-converting enzyme-angiotensin Ⅱ-angiotensin Ⅱ receptor type 1(ACE-AngⅡ-AT1) axis is the classic metabolic pathway of RAS. Angiotensin-converting enzyme 2(ACE2) hydrolyzes AngⅡ to produce Ang(1-7), and Ang(1-7) acts on Mas receptors to relax blood vessels, all of which is the ACE2-Ang(1-7)-Mas axis. The regulatory factors of gene expression and signal transduction may be closely related to the biological control mechanism of different TCM syndromes. The ACE-AngⅡ-AT1 axis, ACE2-Ang(1-7)-Mas axis and the interaction between their targeted miRNAs with internal and external environment may provide a biological foundation to clarify the possible mechanism of the formation of different syndromes of EH, and then to reveal the essence of TCM syndromes of EH.