中医药调控 CD4+ T 细胞亚群防治动脉粥样硬化的研究进展

来源期刊：广州医药 | 24-29 发布时间：2026-01-20 收稿时间：2026/2/6 15:44:14 阅读量：137

作者：: 叶晨,

刘悦,

杨欢,

盖巧稚,

徐月,

李珂珂,

关键词：: 动脉粥样硬化 CD4+ T细胞免疫调节中医药; atherosclerosis CD4+ T cell immunoregulation traditional Chinese medicine

DOI：: 10. 20223 / j. cnki. 1000-8535. 2026. 01. 004

收稿时间：: 2025-06-06
修订日期：
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引用总数：: 0

动脉粥样硬化（AS）是一种起始于炎症介导的内皮损伤的慢性血管疾病，其本质是免疫炎症驱动的病理过程，是众多心血管疾病的病理基础。CD4⁺ T细胞亚群［包括辅助性T细胞1型（T helper 1 cell，Th1）、Th2、Th17、调节性T细胞等］通过分泌特异性细胞因子参与AS的炎症反应，其中促炎性CD4+ T细胞与抗炎性CD4⁺ T细胞的抗炎功能失衡是推动斑块进展的关键环节，在AS斑块形成与发展中起关键作用。近年来，多项研究表明某些中药单体、经典复方及其有效成分，具有多靶点、多层次机制调控CD4⁺ T细胞分化及功能，这些作用共同减轻血管内皮炎症反应、抑制巨噬细胞泡沫化及平滑肌细胞迁移等，延缓AS斑块形成与发展，为AS防治提供了新思路，展现了中医药在该领域的研究展现出独特优势与广阔前景，本文综述了中医药通过干预CD4⁺ T细胞亚群平衡防治AS的最新研究进展，及其影响相关细胞因子网络及关键信号通路的作用机制，为开发具有多靶点协同优势的创新中药与中西医结合治疗方案提供了关键理论依据与实践方向。

Atherosclerosis（AS）is a chronic vascular disease that originates from inflammation mediated endothelial

damage．Its essence is a pathological process driven by immune inflammation，and it is the pathological basis of many cardiovascular diseases．CD4⁺ T cell subsets（including Th1，Th2，Th17，Treg，etc.）participate in the inflammatory response of AS by secreting specific cytokines．The imbalance of anti-inflammatory function between pro-inflammatory CD4⁺ T cells and anti-inflammatory CD4⁺T cells is a key link in promoting plaque progression and playing a crucial role in the formation and development of AS plaques．In recent years，a number of studies have shown that the monomers，classic prescriptions and their effective ingredients of Chinese herbs have the effect of multi-target，multi-level mechanism to regulate the differentiation and function of CD4⁺ T cells．These effects together reduce the inflammatory reaction of vascular endothelium，inhibit the foam formation of macrophages and smooth muscle cell migration，delay the formation and development of AS plaque，provide new ideas for the prevention and treatment of AS，and make the research of Chinese medicine show unique advantages and broad prospects in this field．This article reviews the latest research progress of Chinese medicine in the prevention and treatment of AS by intervening in the balance of CD4⁺ T cell subsets，as well as the mechanism of its effects on related cytokine networks and key signal pathways．This provides a key theoretical basis and practical direction for the development of innovative traditional Chinese medicine and integrated traditional Chinese and Western medicine treatment plans with multi-target synergistic advantages．

动脉粥样硬化（atherosclerosis，AS）是众多心血管疾病的病理基础，AS发生发展始于炎症损伤导致的内皮功能障碍，涉及多种细胞，包括免疫细胞、血管内皮细胞、血管平滑肌细胞等^［1］，其中CD4⁺ T细胞在AS的发生中起重要的调节作用，CD4⁺ T细胞亚群失衡会加速AS的进展^［2-3］。随着病程进展，血管中脂质代谢紊乱加剧了巨噬细胞衍生的泡沫细胞的形成、炎症反应、细胞凋亡及自噬，最终发展为极易破裂的易损斑块，后者诱发血小板聚集和血栓形成，是导致急性冠脉综合征、脑卒中和猝死的直接原因^［4］。即使斑块稳定，其慢性增大也可导致血管管腔的严重狭窄，引发慢性缺血症状。

AS病灶内存在大量活化的免疫细胞浸润，其进展本质上是促炎性T细胞与抗炎性T细胞之间失衡的结果^［5］。AS在早期或斑块稳定时，抗炎性T细胞占优势，以限制炎症的进展。在危险因素（如高脂血症、高血压、吸烟）的持续刺激下，氧化低密度脂蛋白（oxidized low-density lipoprotein，ox-LDL）驱动T细胞活化，导致促炎性T细胞占主导，形成强烈的促炎微环境，促进斑块生长、坏死核心扩大、纤维帽变薄和斑块的最终破裂，引发急性心血管事件^［6］。因此，CD4⁺ T细胞亚群的动态平衡深刻影响着斑块的稳定性与疾病进程。对免疫细胞的研究为AS治疗提供了新思路。通过调节免疫反应，可以抑制疾病进展，减少心血管事件的发生。

1 中医药防治 AS 的理论基础

1.1 中医对AS的认识

AS在中医归属于“胸痹”“脉痹”等范畴，其核心病机为本虚标实之证，以脾虚为本，脾虚致痰瘀互结，阻滞脉络为标^［7］。《医宗必读》言：“脾为生痰之源”。《景岳全书》言：“夫人之多痰，悉由中虚而然……惟是不能食者，反能生痰。此以脾虚不能化食，而食即为痰也”。说明脾虚则运化失职，水谷不化精微反生痰浊脂膏，是“痰浊”产生的核心环节。《丹溪心法》言：“痰挟瘀血，遂成窠囊”。《医林改错》言：“痰涎壅塞气管，气血不得流通”。《血证论》又指出：“血积既久，亦能化为痰水”。当痰浊阻滞脉道，可致血行不畅而成瘀，日久痰瘀互结，凝滞于脉道之中，此病理过程正与现代医学中AS的核心形成机制相契合。这一病理环节深刻揭示了血脉不通、脏腑功能失调的疾病本质，因此在治疗时应采取健脾祛痰化瘀之法。

1.2 中医药“整体观念”及“多靶点干预”的优势

“整体观念”是中医药治疗的核心理念之一，强调人体是一个有机整体，各脏腑、经络、气血相互联系、相互影响。中医药治疗不仅关注局部病变，更注重从整体上调整阴阳平衡、气血运行及脏腑功能等方面，以达到治疗疾病的目的。在治疗AS时需兼顾补脾、活血化瘀和化痰祛湿等方法，从而实现整体调节。近年来，随着中医药现代化研究的深入，中医药在动脉粥样硬化中的作用机制逐渐被揭示。研究发现，黄芩-黄连的主要活性成分槲皮素、汉黄素、β-谷甾醇、黄芩素和小檗碱干预肿瘤坏死因子（tumor necrosis factor，TNF）、白细胞介素-17（interleukin-17，IL-17）、丝裂原活化蛋白激酶和核因子κB（nuclear factor kappa-B，NF-κB）信号通路，并在体外实验中观察到，其部分通过Toll样受体4（toll-like receptor 4，TLR4）/NF-κB降低AS小鼠的炎症水平，从而减少斑块面积，增加斑块稳定性^［8］。另一项研究发现，血府逐瘀汤治疗AS的主要活性成分为槲皮素和β-胡萝卜素，其活性成分可以通过阻断半乳糖凝集素-3/炎症小体3信号通路，并加速脂质降解以减轻AS^［9］。此外，还有痰瘀同治方的主要活性成分黄芩苷、柚皮素和姜黄素可能作用于TNF 等靶点并通过核受体调控脂质代谢、炎症反应和能量平衡通路以对抗AS^［10］。

由此可见，中药的同一活性成分可以调节不同的靶点，同一靶点可以干扰不同的生物过程和信号通路，显示出中医多组分、多靶点、多途径干预的特点。这些研究为中医药在动脉粥样硬化的治疗中提供了坚实的理论基础和科学依据。充分体现了中医“整体观念”与现代医学的“多靶点干预”的高度契合。由于AS的发病机制复杂，涉及多种细胞及途径。因此，中医药凭借其多成分、多靶点的独特优势，已成为防治AS的重要策略。

2 CD4⁺ T 细胞在 AS 中的免疫调控作用

CD4⁺ T细胞亚群在AS的进展中构成了复杂的免疫调控网络，发挥着关键的角色。根据其功能和表面标志物的不同，可分为多个亚群，不同类型的CD4⁺ T细胞亚群通过其独特的功能和信号通路，参与AS进程。

2.1 促炎性CD4⁺ T细胞与AS的关系

促炎性CD4⁺ T细胞通过驱动斑块炎症、促进脂质蓄积、削弱纤维帽结构等作用，最终导致斑块的易损和不稳定^［11］。其中促炎性CD4⁺ T细胞主要包含辅助性T细胞1型（T helper 1 cell，Th1）、Th9、Th17和Th22等亚群。

Th1细胞主要分泌干扰素-γ（interferon-γ，IFN-γ）等促炎因子，促进巨噬细胞向泡沫细胞的转化，从而加速斑块的形成^［12］。此外，IFN-γ还促进巨噬细胞分泌基质金属蛋白酶（mat rix metalloproteinase，MMP），MMP可以降解纤维帽中的胶原蛋白和弹性蛋白，进一步削弱纤维帽的稳定性，导致易损斑块的形成^［13］。升高的IFN-γ与IL-12协同作用，促进CD4⁺ T细胞偏向Th1分化^［14］。Th9细胞主要分泌IL-9等促炎因子，通过上调内皮细胞中血管细胞黏附分子-1的表达，从而促进单核细胞的浸润和斑块的形成^［15］。一项研究发现，在AS小鼠中IL-9的表达水平升高与斑块的形成有关，而阻断IL-9则可以显著减少斑块大小，且血清ox-LDL水平与Th9比例呈正相关，进一步证实了Th9在AS中的致病作用^［16］。Th17主要分泌IL-17A等促炎因子，通过诱导趋化因子的表达促进单核细胞和巨噬细胞的招募，形成并加剧炎症微反应^［17］。IL-17A还可与TNF-α协同作用，促进MMP的表达以降解细胞外基质，进一步加剧斑块不稳定性^［18］。Th22主要分泌IL-22等促炎因子，通过上调MMP以增加细胞活性，降解基底膜并加速低密度脂蛋白的氧化和渗入，并显著增加细胞间黏附分子-1的表达，使单核细胞黏附于内皮细胞，并迁移至内皮下层，从而加速单核细胞向泡沫细胞的转化^［19］。

2.2 抗炎性CD4+ T细胞与AS的进展

抗炎性CD4⁺ T细胞通过分泌抗炎因子和抑制性分子来抑制过度炎症反应、促进抗炎巨噬细胞表型转化、刺激胶原合成、维持免疫耐受，从而抑制斑块发展、增强斑块稳定性的保护。抗炎性CD4⁺ T细胞主要包含调节性T细胞（regulatory T cells，Treg）和Th2等亚群。

Treg主要分泌转化生长因子-β（transforming growth factor-β，TGF-β）和IL-10等抗炎细胞因子，主要抑制T细胞极化为Th1和Th17亚型，并限制其致病活性^［20］。其次，Treg还可以下调巨噬细胞表面的清道夫受体和单核细胞趋化蛋白-1的表达，减少内皮细胞活化和白细胞募集，阻碍单核细胞募集到动脉粥样硬化病变中，抑制巨噬细胞的促炎特性，并促进巨噬细胞活化转变为抗炎表型，从而减轻炎症反应和斑块炎症^［21］。另有研究表明，Treg的数量减少或功能丧失会导致免疫平衡的破坏，从而促进AS的进展^［22］。Th2主要分泌IL-4、IL-5和IL-13等细胞因子。其中IL-4、IL-5可抑制Th1、Th17细胞分化，同时又促进Th2的活化，形成正反馈循环^［23］。IL-5还能够刺激B1细胞产生针对ox-LDL的抗体，从而抑制炎症和坏死核心的形成^［24］。此外，有证据表明AS患者血浆中IL-5水平与冠状动脉狭窄程度呈负相关^［25］。IL-13则通过诱导胶原表达并抑制单核细胞与巨噬细胞的浸润，以稳定动脉粥样硬化斑块^［26］。

2.3 CD4+ T细胞亚群平衡与AS的研究进展

CD4⁺ T细胞的平衡失调是AS的发病的核心免疫机制，其促炎与抗炎平衡决定了斑块的形成、稳定性和炎症反应的持续性^［27］。Th1和Th17驱动血管内皮炎症和斑块不稳定，而Th2和Treg则发挥关键的抗炎和稳定斑块作用。近年来，越来越多的研究聚焦于理解亚群间的平衡调控机制，特别是Th1/Th2和Th17/Treg之间的平衡。

在病变的早期阶段，Th1反应占主导地位，促进斑块的形成；在慢性阶段，Th2反应逐渐增强，对抗Th1反应，促进斑块的稳定。而在多种疾病或危险因素的作用下，如糖尿病、衰老和吸烟的患者中，Th1/Th2的比例均转向Th1优势，导致促炎反应增强，促进AS的进展^［28］。另外，Th17比例增加和Treg细胞比例减少会导致炎症反应的增强，从而促进AS的发生和发展^［29］。在CD4⁺ T细胞激活过程中，各种上游调节因子通过激活腺苷酸活化蛋白激酶（adenosine 5’-monophosphate-activated protein kinase，AMPK）信号通路，显著抑制Th17并上调Treg细胞，以改善Th17/Treg失衡，减轻炎症反应^［30］。因此，靶向调节CD4⁺ T细胞的亚群平衡和功能状态，可能为AS的治疗提供新的策略。

3 中医药调控 CD4⁺ T 细胞防治 AS 的研究进展

中医药通过调控CD4⁺ T细胞来防治AS是一种近年来受到广泛关注的研究方向，其有效成分可以通过调节CD4⁺ T细胞的平衡、抑制炎症反应等作用，达到延缓或逆转斑块进展，其中以健脾祛痰化瘀类中药为主。

3.1 单味中药及活性成分防治AS

丹皮酚是由牡丹皮提取出的天然酚类化合物，Shi等^［31］在AS小鼠实验中发现丹皮酚可以通过调节肠道微生物群来恢复Treg/Th17的平衡，通过下调了α-平滑肌肌动蛋白、MMP-2/9和胶原蛋白I/Ⅲ的表达水平，改善了AS小鼠血管胶原沉积，减轻血管纤维化，以达到防治AS的目的。苦杏仁苷是桃仁的主要成分，Jiang等^［32］研究发现，在APOE-/-小鼠中，能显著降低小鼠血脂水平，升高Treg亚群比例并增加T细胞核心转录因子叉头基因P3（forkhead box P3，Foxp3）表达，从而抑制炎症反应并增强了Treg的免疫调节功能，最终减轻AS斑块负荷并减缓疾病进展。此外，多项研究表明，姜黄、丹参、黄芪等单体中药的有效成分均可通过调节CD4⁺ T细胞亚群的平衡，发挥抗氧化应激、抑制炎症反应等作用，从而达到治疗AS的目的^［33-35］。

3.2 中药复方及活性成分防治AS

在Qiu等^［36］使用养阴清热活血方干预AS小鼠的实验中发现，其可能通过抑制IL-6/信号传导及转录激活蛋白-3（signal transducer and activator of transcription，STAT3）信号传导和恢复IL-2/STAT5信号传导参与Th17和Treg分化的调节。Chen等^［37］发现补阳还五汤可以通过调节TGF-β/Smad2信号通路增加AS小鼠CD4⁺ T细胞中Treg的比例，并调节炎症因子的水平，促进Tregs细胞的外周分化，增加Tregs数量，恢复CD4⁺ T细胞之间的免疫平衡，调节脂质代谢，抑制炎症反应，具有增强斑块稳定性的潜力。Fan等^［38］发现，安宫牛黄丸治疗通过调节维A酸相关孤儿受体γt（retinoid-related orphan nuclear receptor γt ， RORγt）和Foxp3表达纠正了早期AS小鼠模型中Th17/Treg细胞的免疫失衡，抑制促炎介质的释放，促进抗炎因子的释放，下调趋化因子及其受体的表达，从而促进早期AS的抗炎作用。此外，安宫牛黄丸还下调MMP-2、MMP-9的表达，减少胶原纤维并减少巨噬细胞、树突状细胞和血管平滑肌细胞浸润到斑块中，从而促进后者的稳定性。Peng等^［39］在对芪参益气滴丸的AS小鼠模型中发现，其直接抑制斑块区域内的Th17细胞，降低促AS细胞因子IL-17的释放，同时又可加速胆固醇代谢，以此减缓AS进展。

4 结语

大量研究证实：众多中药单体、经典复方，能通过多靶点、多层次作用，显著调节Th1/Th2、Th17/Treg等关键亚群的失衡状态。核心机制涉及抑制CD4⁺ T细胞促炎亚群分化并下调关键转录因子及促炎因子的分泌，从而减轻血管壁炎症浸润与内皮损伤；促进抗炎亚群分化，并上调抗炎因子释放，从而增强免疫耐受，以稳定斑块。这些作用常与抑制ox-LDL摄取、调节巨噬细胞极化、改善脂质代谢等效应协同，共同构成中医药“健脾祛痰”“活血化瘀”等治法防治AS的现代免疫学基础，体现了“整体观念”的中医特色。

CD4⁺ T细胞介导的免疫炎症反应是贯穿AS全过程的核心机制。促炎效应超过抗炎保护作用是斑块进展与不稳定的关键免疫学基础，深入理解Th1、Th17和Treg等亚群在斑块中的复杂相互作用及其调控网络，不仅深化了对AS病理本质的认识，更为开发靶向免疫调节的新型治疗策略提供了理论基础，如调节CD4⁺ T细胞亚群平衡、阻断关键炎症通路、增强Treg功能等。针对这些CD4⁺ T细胞亚群的调控已成为AS免疫治疗的重要策略方向。

1、QIAN%E2%80%83T%EF%BC%8CGUO%E2%80%83D%EF%BC%8CSUN%E2%80%83L%EF%BC%8Cet%E2%80%83al%EF%BC%8ECrosstalk%E2%80%83between%E2%80%83%0Alipid%E2%80%83metabolism%E2%80%83and%E2%80%83macrophages%E2%80%83in%E2%80%83atherosclerosis%EF%BC%9A%0ATherapeutic%E2%80%83potential%E2%80%83of%E2%80%83natural%E2%80%83products%EF%BC%BBJ%EF%BC%BD%EF%BC%8EFront%E2%80%83%0ACardiovasc%E2%80%83Med%EF%BC%8C2025%EF%BC%8812%EF%BC%89%EF%BC%9A1529924%EF%BC%8E

2、CHEN%E2%80%83J%EF%BC%8CXIANG%E2%80%83X%EF%BC%8CNIE%E2%80%83L%EF%BC%8Cet%E2%80%83al%EF%BC%8EThe%E2%80%83emerging%E2%80%83%0Arole%E2%80%83of%E2%80%83Th1%E2%80%83cells%E2%80%83in%E2%80%83atherosclerosis%E2%80%83and%E2%80%83its%E2%80%83implications%E2%80%83%0Afor%E2%80%83therapy%EF%BC%BBJ%EF%BC%BD%EF%BC%8EFront%E2%80%83Immunol%EF%BC%8C2023%EF%BC%8813%EF%BC%89%EF%BC%9A%0A1079668%EF%BC%8E

3、邓智勇，杨崇哲．嗜酸性粒细胞在心血管疾病中的研究进展［J］．广州医药，2025，56（4）：429-438．

4、HE%E2%80%83C%EF%BC%8CKIM%E2%80%83H%E2%80%83I%EF%BC%8CPARK%E2%80%83J%EF%BC%8Cet%E2%80%83al%EF%BC%8EThe%E2%80%83role%E2%80%83of%E2%80%83immune%E2%80%83%0Acells%E2%80%83in%E2%80%83different%E2%80%83stages%E2%80%83of%E2%80%83atherosclerosis%EF%BC%BBJ%EF%BC%BD%EF%BC%8EInt%E2%80%83J%E2%80%83%0AMed%E2%80%83Sci%EF%BC%8C2024%EF%BC%8C21%EF%BC%886%EF%BC%89%EF%BC%9A1129-1143%EF%BC%8E

5、TAN%E2%80%83L%EF%BC%8CXU%E2%80%83Q%EF%BC%8CSHI%E2%80%83R%EF%BC%8Cet%E2%80%83al%EF%BC%8EBioinformatics%E2%80%83%0Aanalysis%E2%80%83%20reveals%E2%80%83%20the%E2%80%83%20landscape%E2%80%83%20of%E2%80%83%20immune%E2%80%83%20cell%E2%80%83%0Ainfiltration%E2%80%83and%E2%80%83immune-related%E2%80%83pathways%E2%80%83participating%E2%80%83%0Ain%E2%80%83the%E2%80%83progression%E2%80%83of%E2%80%83carotid%E2%80%83atherosclerotic%E2%80%83plaques%0A%EF%BC%BBJ%EF%BC%BD%EF%BC%8EArtif%E2%80%83Cells%E2%80%83Nanomed%E2%80%83Biotechnol%EF%BC%8C2021%EF%BC%8C49%0A%EF%BC%881%EF%BC%89%EF%BC%9A96-107%EF%BC%8E

6、%E5%BC%A0%E7%91%B6%EF%BC%8C%E6%9D%A8%E6%99%8B%E9%9D%99%EF%BC%8C%E5%88%98%E9%9D%99%E7%A5%8E%EF%BC%8C%E7%AD%89%EF%BC%8E%E2%80%83PCSK9%E5%9C%A8%E5%8A%A8%E8%84%89%E7%B2%A5%E6%A0%B7%E7%A1%AC%E5%8C%96%E6%80%A7%E5%BF%83%E8%A1%80%E7%AE%A1%E7%96%BE%E7%97%85%E4%BD%9C%E7%94%A8%E6%9C%BA%E5%88%B6%E4%B8%AD%E7%9A%84%E7%A0%94%E7%A9%B6%E8%BF%9B%E5%B1%95%EF%BC%BBJ%EF%BC%BD%20%EF%BC%8E%E4%B8%AD%E5%9B%BD%E5%8C%BB%E5%B8%88%E6%9D%82%E5%BF%97%EF%BC%8C2023%EF%BC%8C25%EF%BC%888%EF%BC%89%EF%BC%9A1260-1264%EF%BC%8E

7、梁清芝，陈正涛，冷玉琳，等．基于“虚气留滞”理论探讨血管内皮细胞自噬对糖尿病大血管病变的影响［J］．中国实验方剂学杂志，2023，29（3）：178-185．

8、JI%E2%80%83L%EF%BC%8CSONG%E2%80%83T%EF%BC%8CGE%E2%80%83C%EF%BC%8Cet%E2%80%83al%EF%BC%8EIdentification%E2%80%83%20of%E2%80%83%0Abioactive%E2%80%83%20compounds%E2%80%83%20and%E2%80%83%20potential%E2%80%83%20mechanisms%E2%80%83%20of%E2%80%83%0Ascutellariae%E2%80%83%20radix-coptidis%E2%80%83%20rhizoma%E2%80%83in%E2%80%83the%E2%80%83treatment%E2%80%83of%E2%80%83%0Aatherosclerosis%E2%80%83%20by%E2%80%83integrating%E2%80%83%20network%E2%80%83%20pharmacology%E2%80%83%0Aand%E2%80%83experimental%E2%80%83validation%EF%BC%BBJ%EF%BC%BD%EF%BC%8EBi%20o%20m%20e%20d%E2%80%83%0APharmacother%EF%BC%8C2023%EF%BC%88165%EF%BC%89%EF%BC%9A115210%EF%BC%8E

9、YUAN%E2%80%83J%EF%BC%8CYAN%E2%80%83F%EF%BC%8CLI%E2%80%83W%EF%BC%8Cet%E2%80%83al%EF%BC%8EN%20e%20t%20w%20o%20r%20k%E2%80%83%0Apharmacological%E2%80%83%20analysis%E2%80%83%20of%E2%80%83Xuefu%E2%80%83%20Zhuyu%E2%80%83%20decoction%E2%80%83%0Ain%E2%80%83the%E2%80%83treatment%E2%80%83of%E2%80%83atherosclerosis%EF%BC%BBJ%EF%BC%BD%EF%BC%8EFront%E2%80%83%0APharmacol%EF%BC%8C2022%EF%BC%8813%EF%BC%89%EF%BC%9A1069704%EF%BC%8E

10、DAI%E2%80%83J%EF%BC%8CZHOU%E2%80%83X%EF%BC%8CXU%E2%80%83X%EF%BC%8Cet%E2%80%83al%EF%BC%8EStudy%E2%80%83%20on%E2%80%83%20the%E2%80%83%0Aanti-atherosclerosis%E2%80%83mechanisms%E2%80%83%20of%E2%80%83%20Tanyu%E2%80%83%20Tongzhi%E2%80%83%0Aformula%E2%80%83based%E2%80%83on%E2%80%83network%E2%80%83pharmacology%EF%BC%8CMendelian%E2%80%83%0Arandomization%EF%BC%8Cand%E2%80%83experimental%E2%80%83verification%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0APharm%E2%80%83Biol%EF%BC%8C2024%EF%BC%8C62%EF%BC%881%EF%BC%89%EF%BC%9A790-802%EF%BC%8E

11、RAZEGHIAN-JAHROMI%E2%80%83I%EF%BC%8CKARIMI%E2%80%83AKHORMEH%E2%80%83A%EF%BC%8CRAZMKHAH%E2%80%83M%EF%BC%8Cet%E2%80%83al%EF%BC%8EImmune%E2%80%83%20system%E2%80%83%20and%E2%80%83%0Aatherosclerosis%EF%BC%9AHostile%E2%80%83or%E2%80%83friendly%E2%80%83relationship%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0AInt%E2%80%83J%E2%80%83Immunopathol%E2%80%83Pharmacol%EF%BC%8C2022%EF%BC%8836%EF%BC%89%EF%BC%9A%0A3946320221092188%EF%BC%8E

12、CAI%E2%80%83D%EF%BC%8CLIU%E2%80%83H%EF%BC%8CWANG%E2%80%83J%EF%BC%8Cet%E2%80%83al%EF%BC%8EBalasubramide%E2%80%83%0Ad%20e%20ri%20v%20ati%20v%20e%E2%80%83%203C%E2%80%83%20att%20e%20n%20u%20at%20e%20s%E2%80%83%20at%20h%20e%20r%20o%20s%20cl%20e%20r%20o%20si%20s%E2%80%83%20i%20n%E2%80%83%0Aapolipoprotein%E2%80%83E-deficient%E2%80%83mice%EF%BC%9ARole%E2%80%83of%E2%80%83AMPK%02STAT1-STING%E2%80%83signaling%E2%80%83pathway%EF%BC%BBJ%EF%BC%BD%EF%BC%8EAging%0A%EF%BC%88Albany%E2%80%83NY%EF%BC%89%EF%BC%8C2021%EF%BC%8C13%EF%BC%888%EF%BC%89%EF%BC%9A12160-12178%EF%BC%8E

13、%E2%80%83%20FEI%E2%80%83J%E2%80%83L%EF%BC%8CLIANG%E2%80%83B%EF%BC%8CJIANG%E2%80%83C%E2%80%83Z%EF%BC%8Cet%E2%80%83al%EF%BC%8ELuteolin%E2%80%83%0Ainhibits%E2%80%83IL-1%CE%B2-induced%E2%80%83%20inflammation%E2%80%83%20in%E2%80%83%20rat%E2%80%83%0Achondrocytes%E2%80%83and%E2%80%83attenuates%E2%80%83osteoarthritis%E2%80%83progression%E2%80%83%0Ain%E2%80%83a%E2%80%83rat%E2%80%83model%EF%BC%BBJ%EF%BC%BD%EF%BC%8EBiomed%E2%80%83Pharmacother%EF%BC%8C2019%0A%EF%BC%88109%EF%BC%89%EF%BC%9A1586-1592%EF%BC%8E

14、%E2%80%83%20CHANG%E2%80%83X%EF%BC%8CZHAO%E2%80%83J%EF%BC%8CZHOU%E2%80%83Y%EF%BC%8Cet%E2%80%83al%EF%BC%8EmiR-7%E2%80%83%0Adeficiency%E2%80%83promotes%E2%80%83Th1%E2%80%83polarization%E2%80%83of%E2%80%83CD4%2BT%E2%80%83cells%E2%80%83%0Aand%E2%80%83%20enhances%E2%80%83the%E2%80%83%20antitumor%E2%80%83%20effect%E2%80%83in%E2%80%83%20adoptive%E2%80%83%20cell%E2%80%83%0Atherapy%E2%80%83for%E2%80%83lung%E2%80%83cancer%EF%BC%BBJ%EF%BC%BD%EF%BC%8EImmunol%E2%80%83Res%EF%BC%8C2024%EF%BC%8C%0A72%EF%BC%881%EF%BC%89%EF%BC%9A134-146%EF%BC%8E

15、%E2%80%83%20YIN%E2%80%83J%E2%80%83J%EF%BC%8CHU%E2%80%83X%E2%80%83Q%EF%BC%8CMAO%E2%80%83Z%E2%80%83F%EF%BC%8Cet%E2%80%83al%EF%BC%8ENeutralization%E2%80%83%0Aof%E2%80%83interleukin-9%E2%80%83%20decreasing%E2%80%83mast%E2%80%83cells%E2%80%83infiltration%E2%80%83in%E2%80%83%0Aexperimental%E2%80%83autoimmune%E2%80%83encephalomyelitis%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0AChin%E2%80%83Med%E2%80%83J%EF%BC%88Engl%EF%BC%89%EF%BC%8C2017%EF%BC%8C130%EF%BC%888%EF%BC%89%EF%BC%9A964-971%EF%BC%8E

16、%E2%80%83%20LI%E2%80%83Q%EF%BC%8CMING%E2%80%83T%EF%BC%8CWANG%E2%80%83Y%EF%BC%8Cet%E2%80%83al%EF%BC%8EIncreased%E2%80%83%20Th9%E2%80%83%0Acells%E2%80%83and%E2%80%83%20IL-9%E2%80%83levels%E2%80%83accelerate%E2%80%83disease%E2%80%83progression%E2%80%83in%E2%80%83%0Aexperimental%E2%80%83atherosclerosis%EF%BC%BBJ%EF%BC%BD%EF%BC%8EAm%E2%80%83J%E2%80%83Transl%E2%80%83Res%EF%BC%8C%0A2017%EF%BC%8C9%EF%BC%883%EF%BC%89%EF%BC%9A1335-1343%EF%BC%8E

17、REECE%E2%80%83M%E2%80%83D%EF%BC%8CTAYLOR%E2%80%83R%E2%80%83R%EF%BC%8CSONG%E2%80%83C%EF%BC%8Cet%E2%80%83al%EF%BC%8ETargeting%E2%80%83%0Amacrophage%E2%80%83dysregulation%E2%80%83for%E2%80%83viral%E2%80%83infections%EF%BC%9ANovel%E2%80%83%0Atargets%E2%80%83for%E2%80%83immunomodulators%EF%BC%BBJ%EF%BC%BD%EF%BC%8EFront%E2%80%83Immunol%EF%BC%8C%0A2021%EF%BC%8812%EF%BC%89%EF%BC%9A768695%EF%BC%8E

18、%E2%80%83%20KOURI%E2%80%83V%E2%80%83P%EF%BC%8COLKKONEN%E2%80%83J%EF%BC%8CNURMI%E2%80%83K%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AIL-17A%E2%80%83%20and%E2%80%83%20TNF%E2%80%83%20synergistically%E2%80%83%20drive%E2%80%83%20expression%E2%80%83%0Aof%E2%80%83%20proinflammatory%E2%80%83mediators%E2%80%83in%E2%80%83%20synovial%E2%80%83fibroblasts%E2%80%83%0Avia%E2%80%83I%CE%BAB%CE%B6-dependent%E2%80%83induction%E2%80%83of%E2%80%83ELF3%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0ARheumatology%EF%BC%88Oxford%EF%BC%89%EF%BC%8C2023%EF%BC%8C62%EF%BC%882%EF%BC%89%EF%BC%9A872-%0A885%EF%BC%8E

19、SHI%E2%80%83L%EF%BC%8CJI%E2%80%83Q%EF%BC%8CLIU%E2%80%83L%EF%BC%8Cet%E2%80%83al%EF%BC%8EIL-22%E2%80%83%20produced%E2%80%83%20by%E2%80%83%0ATh22%E2%80%83%20cells%E2%80%83%20aggravates%E2%80%83%20atherosclerosis%E2%80%83%20development%E2%80%83%0Ain%E2%80%83ApoE-%2F-%E2%80%83%20mice%E2%80%83%20by%E2%80%83%20enhancing%E2%80%83DC-induced%E2%80%83%20Th17%E2%80%83%0Acell%E2%80%83proliferation%EF%BC%BBJ%EF%BC%BD%EF%BC%8EJ%E2%80%83Cell%E2%80%83Mol%E2%80%83Med%EF%BC%8C2020%EF%BC%8C24%0A%EF%BC%885%EF%BC%89%EF%BC%9A3064-3078%EF%BC%8E

20、TIAN%E2%80%83H%EF%BC%8CXING%E2%80%83J%EF%BC%8CTANG%E2%80%83X%EF%BC%8Cet%E2%80%83al%EF%BC%8ECytokine%E2%80%83%0Anetwo%20r%20k%20s%E2%80%83%20p%20rovi%20de%E2%80%83%20s%20ufficie%20nt%E2%80%83%20evi%20de%20nce%E2%80%83%20fo%20r%E2%80%83%20t%20he%E2%80%83%0Adifferentiation%E2%80%83of%E2%80%83CD4%2B%E2%80%83T%E2%80%83cells%E2%80%83in%E2%80%83teleost%E2%80%83fish%EF%BC%BBJ%EF%BC%BD%EF%BC%8EDev%E2%80%83Comp%E2%80%83Immunol%EF%BC%8C2023%EF%BC%88141%EF%BC%89%EF%BC%9A104627%EF%BC%8E

21、AIT-OUFELLA%E2%80%83H%EF%BC%8CLAVILLEGRAND%E2%80%83J%E2%80%83R%EF%BC%8CTEDGUI%E2%80%83%0AA%EF%BC%8ERegulatory%E2%80%83%20T%E2%80%83%20cell-enhancing%E2%80%83therapies%E2%80%83to%E2%80%83treat%E2%80%83%0Aatherosclerosis%EF%BC%BBJ%EF%BC%BD%EF%BC%8ECells%EF%BC%8C2021%EF%BC%8C10%EF%BC%884%EF%BC%89%EF%BC%9A723%EF%BC%8E

22、%E2%80%83WANG%E2%80%83X%EF%BC%8CZHOU%E2%80%83H%EF%BC%8CLIU%E2%80%83Q%EF%BC%8Cet%E2%80%83al%EF%BC%8ETargeting%E2%80%83%0Aregulatory%E2%80%83T%E2%80%83cells%E2%80%83for%E2%80%83cardiovascular%E2%80%83diseases%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0AFront%E2%80%83Immunol%EF%BC%8C2023%EF%BC%8814%EF%BC%89%EF%BC%9A1126761%EF%BC%8E

23、%E2%80%83FERN%20%C3%81%20NDEZ-GALLEGO%E2%80%83N%EF%BC%8CCASTILLO%02GONZ%C3%81LEZ%E2%80%83R%EF%BC%8CM%C3%89NDEZ-BARBERO%E2%80%83N%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AThe%E2%80%83impact%E2%80%83of%E2%80%83type%E2%80%832%E2%80%83immunity%E2%80%83and%E2%80%83allergic%E2%80%83diseases%E2%80%83in%E2%80%83%0Aatherosclerosis%EF%BC%BBJ%EF%BC%BD%EF%BC%8EAllergy%EF%BC%8C2022%EF%BC%8C77%EF%BC%8811%EF%BC%89%EF%BC%9A%0A3249-3266%EF%BC%8E

24、%E2%80%83%20TSIANTOULAS%E2%80%83D%EF%BC%8CDIEHL%E2%80%83C%E2%80%83J%EF%BC%8CWITZTUM%E2%80%83J%E2%80%83L%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AB%E2%80%83cells%E2%80%83and%E2%80%83humoral%E2%80%83immunity%E2%80%83in%E2%80%83atherosclerosis%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0ACirc%E2%80%83Res%EF%BC%8C2014%EF%BC%8C114%EF%BC%8811%EF%BC%89%EF%BC%9A1743-1756%EF%BC%8E

25、YE%E2%80%83D%EF%BC%8CWANG%E2%80%83Z%EF%BC%8CYE%E2%80%83J%EF%BC%8Cet%E2%80%83al%EF%BC%8EInterleukin-5%E2%80%83levels%E2%80%83%0Aare%E2%80%83decreased%E2%80%83in%E2%80%83the%E2%80%83plasma%E2%80%83of%E2%80%83coronary%E2%80%83artery%E2%80%83disease%E2%80%83%0Apatients%E2%80%83and%E2%80%83inhibit%E2%80%83Th1%E2%80%83and%E2%80%83Th17%E2%80%83%20differentiation%E2%80%83in%E2%80%83%0Avitro%EF%BC%BBJ%EF%BC%BD%EF%BC%8ERev%E2%80%83Esp%E2%80%83Cardiol%EF%BC%88Engl%E2%80%83Ed%EF%BC%89%EF%BC%8C2020%EF%BC%8C73%0A%EF%BC%885%EF%BC%89%EF%BC%9A393-402%EF%BC%8E

26、%E2%80%83%20SAIGUSA%E2%80%83R%EF%BC%8CWINKELS%E2%80%83H%EF%BC%8CLEY%E2%80%83K%EF%BC%8ET%E2%80%83cell%E2%80%83subsets%E2%80%83%0Aand%E2%80%83functions%E2%80%83in%E2%80%83atherosclerosis%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83%20Rev%E2%80%83%0ACardiol%EF%BC%8C2020%EF%BC%8817%EF%BC%89%EF%BC%9A387-401%EF%BC%8E

27、%E2%80%83%20FAN%E2%80%83H%E2%80%83M%EF%BC%8CQIAO%E2%80%83Y%E2%80%83L%EF%BC%8CLIU%E2%80%83Y%EF%BC%8Cet%E2%80%83al%EF%BC%8ELong%02term%E2%80%83%20consequences%E2%80%83%20of%E2%80%83%20regulatory%E2%80%83%20T-cell-specific%E2%80%83%0Aknockout%E2%80%83of%E2%80%83Notch2%E2%80%83in%E2%80%83immune%E2%80%83homeostasis%EF%BC%BBJ%EF%BC%BD%EF%BC%8EInt%E2%80%83%0AImmunopharmacol%EF%BC%8C2023%EF%BC%88124%EF%BC%89%EF%BC%9A111069%EF%BC%8E

28、%E2%80%83%20GRIEVINK%E2%80%83H%E2%80%83W%EF%BC%8CSMIT%E2%80%83V%EF%BC%8CHUISMAN%E2%80%83B%E2%80%83W%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0ACardiovascular%E2%80%83risk%E2%80%83factors%EF%BC%9AThe%E2%80%83effects%E2%80%83of%E2%80%83ageing%E2%80%83and%E2%80%83%0Asmoking%E2%80%83on%E2%80%83the%E2%80%83immune%E2%80%83system%EF%BC%8Can%E2%80%83%20observational%E2%80%83%0Aclinical%E2%80%83study%EF%BC%BBJ%EF%BC%BD%EF%BC%8EFront%E2%80%83Immunol%EF%BC%8C2022%EF%BC%8813%EF%BC%89%EF%BC%9A%0A968815%EF%BC%8E

29、%E2%80%83%20TAHTOUH%E2%80%83ZAATAR%E2%80%83M%EF%BC%8COTHMAN%E2%80%83R%EF%BC%8CABOU%E2%80%83%0ASAMRA%E2%80%83E%EF%BC%8Cet%E2%80%83al%EF%BC%8EExploring%E2%80%83%20the%E2%80%83%20link%E2%80%83%20between%E2%80%83%0AT-regulatory%E2%80%83%20cells%E2%80%83%20and%E2%80%83inflammatory%E2%80%83%20cytokines%E2%80%83in%E2%80%83%0Aatherogenesis%EF%BC%9AFindings%E2%80%83from%E2%80%83%20patients%E2%80%83%20with%E2%80%83%20stable%E2%80%83%0Aangina%E2%80%83pectoris%EF%BC%BBJ%EF%BC%BD%EF%BC%8EAnn%E2%80%83Med%E2%80%83Surg%EF%BC%88Lond%EF%BC%89%EF%BC%8C%0A2024%EF%BC%8C86%EF%BC%888%EF%BC%89%EF%BC%9A4456-4462%EF%BC%8E

30、%E2%80%83%20CHANG%E2%80%83S%EF%BC%8CWANG%E2%80%83Z%EF%BC%8CAN%E2%80%83T%EF%BC%8ET-cell%E2%80%83%20metabolic%E2%80%83%0Areprogramming%E2%80%83in%E2%80%83atherosclerosis%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0ABiomedicines%EF%BC%8C2024%EF%BC%8C12%EF%BC%888%EF%BC%89%EF%BC%9A1844%EF%BC%8E

31、SHI%E2%80%83X%EF%BC%8CHUANG%E2%80%83H%EF%BC%8CZHOU%E2%80%83M%EF%BC%8Cet%E2%80%83al%EF%BC%8EPaeonol%E2%80%83attenuated%E2%80%83vascular%E2%80%83fibrosis%E2%80%83through%E2%80%83regulating%E2%80%83treg%2F%0ATh17%E2%80%83balance%E2%80%83in%E2%80%83a%E2%80%83gut%E2%80%83microbiota-dependent%E2%80%83manner%0A%EF%BC%BBJ%EF%BC%BD%EF%BC%8EFront%E2%80%83Pharmacol%EF%BC%8C2021%EF%BC%8812%EF%BC%89%EF%BC%9A765482%EF%BC%8E

32、DENG%E2%80%83J%EF%BC%8CLI%E2%80%83C%EF%BC%8CWANG%E2%80%83H%EF%BC%8Cet%E2%80%83al%EF%BC%8EAmygdalin%E2%80%83%0Amediates%E2%80%83%20relieved%E2%80%83atherosclerosis%E2%80%83in%E2%80%83apolipoprotein%E2%80%83E%E2%80%83%0Adeficient%E2%80%83mice%E2%80%83through%E2%80%83the%E2%80%83induction%E2%80%83of%E2%80%83%20regulatory%E2%80%83T%E2%80%83%0Acells%EF%BC%BBJ%EF%BC%BD%EF%BC%8EBiochem%E2%80%83Biophys%E2%80%83Res%E2%80%83Commun%EF%BC%8C2011%EF%BC%8C%0A411%EF%BC%883%EF%BC%89%EF%BC%9A523-529%EF%BC%8E

33、%E2%80%83%20GAO%E2%80%83S%EF%BC%8CZHANG%E2%80%83W%EF%BC%8CZHAO%E2%80%83Q%EF%BC%8Cet%E2%80%83al%EF%BC%8ECurcumin%E2%80%83%0Aameliorates%E2%80%83atherosclerosis%E2%80%83in%E2%80%83apolipoprotein%E2%80%83E%E2%80%83deficient%E2%80%83%0Aasthmatic%E2%80%83mice%E2%80%83by%E2%80%83%20regulating%E2%80%83the%E2%80%83balance%E2%80%83of%E2%80%83Th2%2FTreg%E2%80%83%0Acells%EF%BC%BBJ%EF%BC%BD%EF%BC%8EPhytomedicine%EF%BC%8C2019%EF%BC%8852%EF%BC%89%EF%BC%9A129-135%EF%BC%8E

34、曾妮，许妹萍，庄丽明．丹参素对大鼠动脉粥样硬化的作用及其机制［J］．免疫学杂志，2020，36 （10）：884-889，896．

35、%E2%80%83XIN%E2%80%83L%EF%BC%8CGAO%E2%80%83J%EF%BC%8CLIN%E2%80%83H%EF%BC%8Cet%E2%80%83al%EF%BC%8ER%20e%20g%20ul%20at%20o%20r%20y%E2%80%83%0Amechanisms%E2%80%83of%E2%80%83baicalin%E2%80%83in%E2%80%83cardiovascular%E2%80%83diseases%EF%BC%9A%0AA%E2%80%83review%EF%BC%BBJ%EF%BC%BD%EF%BC%8EFront%E2%80%83Pharmacol%EF%BC%8C2020%EF%BC%8811%EF%BC%89%EF%BC%9A%0A583200%EF%BC%8E

36、%E2%80%83%20QIU%E2%80%83R%EF%BC%8CLONG%E2%80%83J%EF%BC%8CZHOU%E2%80%83L%EF%BC%8Cet%E2%80%83al%EF%BC%8EYangyin%E2%80%83Qingre%E2%80%83%0AHuoxue%E2%80%83%20method%E2%80%83%20in%E2%80%83%20traditional%E2%80%83%20Chinese%E2%80%83%20medicine%E2%80%83%0Aameliorates%E2%80%83atherosclerosis%E2%80%83in%E2%80%83ApoE-%2F-%E2%80%83Mice%E2%80%83suffering%E2%80%83%0Afrom%E2%80%83high-fat%E2%80%83diet%E2%80%83and%E2%80%83HSP65%E2%80%83aggression%EF%BC%BBJ%EF%BC%BD%EF%BC%8EEvid%E2%80%83%0ABased%E2%80%83Complement%E2%80%83Alternat%E2%80%83Med%EF%BC%8C2019%EF%BC%882019%EF%BC%89%EF%BC%9A%0A2531979%EF%BC%8E

37、%E2%80%83%20CHEN%E2%80%83S%EF%BC%8CWANG%E2%80%83Y%EF%BC%8CLIANG%E2%80%83C%EF%BC%8Cet%E2%80%83al%EF%BC%8EBuyang%E2%80%83%0AHuanwu%E2%80%83Decoction%E2%80%83%20ameliorates%E2%80%83%20atherosclerosis%E2%80%83%20by%E2%80%83%0Aregulating%E2%80%83TGF-%CE%B2%2FSmad2%E2%80%83%20pathway%E2%80%83%20to%E2%80%83%20p%20romote%E2%80%83%0Athe%E2%80%83differentiation%E2%80%83of%E2%80%83regulatory%E2%80%83T%E2%80%83cells%EF%BC%BBJ%EF%BC%BD%EF%BC%8EJ%E2%80%83%0AEthnopharmacol%EF%BC%8C2021%EF%BC%88269%EF%BC%89%EF%BC%9A113724%EF%BC%8E

38、FAN%E2%80%83Q%EF%BC%8CLIU%E2%80%83Y%EF%BC%8CRAO%E2%80%83J%EF%BC%8Cet%E2%80%83al%EF%BC%8EAnti-atherosclerosis%E2%80%83%0Aeffect%E2%80%83of%E2%80%83Angong%E2%80%83Niuhuang%E2%80%83Pill%E2%80%83via%E2%80%83regulating%E2%80%83Th17%2FTreg%E2%80%83%0Aimmune%E2%80%83balance%E2%80%83and%E2%80%83inhibiting%E2%80%83chronic%E2%80%83inflammatory%E2%80%83%0Aon%E2%80%83%20ApoE-%2F-%E2%80%83%20mice%E2%80%83%20model%E2%80%83%20of%E2%80%83%20early%E2%80%83%20and%E2%80%83%20mid-term%E2%80%83%0Aatherosclerosis%EF%BC%BBJ%EF%BC%BD%EF%BC%8EFront%E2%80%83Pharmacol%EF%BC%8C2020%0A%EF%BC%8810%EF%BC%89%EF%BC%9A1584%EF%BC%8E

39、%E2%80%83%20PENG%E2%80%83L%EF%BC%8CLV%E2%80%83C%E2%80%83S%EF%BC%8CZHAO%E2%80%83Y%EF%BC%8Cet%E2%80%83al%EF%BC%8EQiShenYiQi%E2%80%83%0Apill%E2%80%83attenuates%E2%80%83atherosclerosis%E2%80%83by%E2%80%83promoting%E2%80%83%20regulatory%E2%80%83%0AT%E2%80%83cells%EF%BC%8Cinhibiting%E2%80%83T%E2%80%83helper%E2%80%8317%E2%80%83cells%E2%80%83and%E2%80%83accelerating%E2%80%83%0Acholesterol%E2%80%83excretion%EF%BC%BBJ%EF%BC%BD%EF%BC%8EOncotarget%EF%BC%8C2017%EF%BC%8C8%0A%EF%BC%8847%EF%BC%89%EF%BC%9A82196-82206%EF%BC%8E

1、国家自然科学基金项目（81703970）；辽宁省自然科学基金优秀青年基金计划项目（2023JH3/10200016）()