基于"肾虚血瘀"理论探讨血管紧张素转换酶2调控缺血性脑卒中研究进展OA
Research Progress on Exploring the Regulation of Angiotensin-Converting Enzyme 2 in Ischemic Stroke Based on the Theory of"Kidney Deficiency and Blood Stasis"
缺血性脑卒中的发病机制与肾素-血管紧张素系统(renin-angiotensin system,RAS)失衡密切相关.血管紧张素转换酶2(angiotensin-converting enzyme 2,ACE2)作为 RAS 的关键调节因子,其功能失调会导致氧化应激、炎症反应及血脑屏障破坏,加剧脑缺血损伤.中医"肾虚血瘀"理论提出肾精亏虚致气血瘀阻脑络,与现代 ACE2 表达下调导致的 RAS 失调高度契合.然而,当前该领域的交叉研究仍存在以下问题:(1)证候与靶点机制关联不深:"肾虚血瘀"宏观证候与 ACE2 表达/功能下调之间,缺乏直接、特异性的分子桥梁阐释;(2)证候生物学定量化依据缺失:尚无基于"肾虚血瘀"证患者的大样本临床研究,无法系统分析证候程度、亚型与血/组织 ACE2 水平等量化指标的相关性,制约了中医证候现代生物学分型标准的建立;(3)中药多靶点网络机制解析不足:多数研究停留在表型观察与单通路验证(如 ACE2 蛋白表达),对中药如何通过"多成分-多靶点-多通路"网络协同调控 ACE2/RAS 轴及下游神经血管单元稳态的系统性研究严重匮乏;(4)中西医结合评价体系有待完善:当前缺血性脑卒中评价多侧重西医神经功能缺损,缺乏融合中医证候动态演变的综合评价体系,且高等级循证医学证据不足.未来,亟须整合多组学技术与"肾虚血瘀"特异性动物模型,深度解析"肾虚-血瘀-ACE2 失调-脑损伤"的因果反馈网络;同时,开展大样本临床研究以锚定证候量化指标,并设计严谨的 RCT 试验,针对缺血性脑卒中不同阶段(急性期、恢复期、二级预防)评估中西医结合方案的疗效与安全性,最终构建融合中西医核心指标的综合评价体系.
The pathogenesis of ischemic stroke(IS)is closely associated with dysregulation of the renin-angiotensin system(RAS).Angiotensin-converting enzyme 2(ACE2)as a key regulator of the RAS,when dysfunctional,leads to oxidative stress,inflammatory re-sponses,and disruption of the blood-brain barrier,thereby exacerbating cerebral ischemic injury.The TCM theory of"kidney deficiency and blood stasis"proposes that deficiency of kidney essence results in qi and blood stagnation obstructing the cerebral collaterals,which closely parallels the RAS dysregulation induced by downregulation of ACE2 expression in modern medicine.However,cross-disciplinary research in this field still faces the following challenges:(1)Superficial correlation between TCM syndrome and mechanistic targets:There is a lack of a direct and specific molecular bridge linking the macroscopic syndrome of"kidney deficiency and blood stasis"to the downregulation of ACE2 expression/function;(2)Absence of quantitative biological evidence for TCM syndromes:No large-scale clinical studies have been conducted based on patients with"kidney deficiency and blood stasis"syndrome,leaving the correlation be-tween syndrome severity/subtype and quantitative indicators such as blood or tissue ACE2 levels unanalyzed,thus hindering the estab-lishment of modern biological subtyping standards for TCM syndromes;(3)Insufficient analysis of the multi-target network mechanisms of Chinese medicinals:Most studies remain at the level of phenotypic observation and single-pathway validation(e.g.,ACE2 protein expression).There is a serious lack of systematic research on how Chinese medicinals coordinately regulate the ACE2/RAS axis and downstream neurovascular unit homeostasis via a"multi-component,multi-target,multi-pathway"network;(4)Incomplete integrated e-valuation system for traditional Chinese and Western medicine:Current IS evaluations predominantly focus on Western neurological defi-cit scales,lacking a comprehensive assessment system that incorporates the dynamic evolution of TCM syndromes.Moreover,high-level evidence-based medical evidence is insufficient.Therefore,future research should urgently integrate multi-omics technologies with"kid-ney deficiency and blood stasis"-specific animal models to deeply dissect the causal feedback network of"kidney deficiency-blood sta-sis-ACE2 dysregulation-brain injury."At the same time,it is necessary to conduct large-scale clinical studies to identify quantitative bi-omarkers for syndromes,along with rigorous randomized controlled trials(RCTs)to evaluate the efficacy and safety of integrated TCM-Western medicine approaches at different stages of IS(acute phase,recovery phase,and secondary prevention).Ultimately,an integrat-ed evaluation system incorporating core indicators from both TCM and Western medicine should be established.
杨巧芳;王谨敏
福建中医药大学,福建 福州 350122福建中医药大学附属第二人民医院,福建 福州 350001
医药卫生
缺血性脑卒中血管紧张素转换酶2"肾虚血瘀"理论肾-脑轴
ischemic stroke(IS)angiotensin-converting enzyme 2(ACE2)the theory of"kidney deficiency and blood stasis"kid-ney-brain axis
《河南中医》 2026 (6)
857-863,7
福建省自然科学基金项目(2022J01832)福建省重大科技创新"揭榜挂帅"专项项目(XJB2022003-2)福建省民间中医药学术传承专项课题项目(XMJ2023023)
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