动脉粥样硬化(AS)是心血管疾病的病理基础,口腔与肠道通过菌群移位、代谢互作及免疫联动共同构成口腔-肠道微生物轴,其稳态失衡通过菌群易位、代谢紊乱和屏障损伤等促进AS发生发展。中医药以整体观念与辨证论治为指导,多靶点调控口腔-肠道微生物平衡,抑制血管炎症与脂质沉积,发挥抗AS效应。本文系统阐述口腔-肠道微生物与AS的关联,探讨中医药调控微生态防治该病的研究进展,分析当前研究存在的局限并展望未来方向,为中医药防治AS提供新的思路与理论依据。
Atherosclerosis (AS) is the pathological basis of cardiovascular diseases. The oral cavity and the gut together constitute the oral-gut microbial axis through microbial translocation, metabolic interactions, and immune crosstalk. Dysbiosis of this axis promotes the occurrence and development of AS via bacterial translocation, metabolic disorders, and barrier damage. Guided by the holistic concept and syndrome differentiation-based treatment, traditional Chinese medicine (TCM) exerts anti-AS effects by multi-target regulation of the oral-gut microbial balance, inhibiting vascular inflammation and lipid deposition. This article systematically elaborates the association between the oral-gut microbiota and AS, explores the research progress of TCM in modulating microecology for the prevention and treatment of AS, analyzes the limitations of current studies, and prospects future directions, so as to provide new insights and theoretical basis for TCM in preventing and treating AS.
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 endothelialdamage.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.
目的 探讨载脂蛋白E(ApoE)基因多态性与卒中后认知障碍的相关性,即大动脉粥样硬化型脑梗塞的严重程度。方法 采用病例——对照研究的方法,收集九江学院附属医院神经内科的100例急性缺血性脑卒中且病因分型为大动脉粥样硬化型患者(脑梗死组)和50例性别、年龄匹配的非缺血性脑卒中患者(对照组)。检测患者的 ApoE 基因型、血脂、美国国立卫生院卒中量表(NIHSS)、卒中后6个月简易智力状态检查量表(MMSE)等,采用多因素方差分析等统计学方法分析他们之间的关联性。结果 ApoE 3/4基因型频率与Ɛ3、Ɛ4等位基因频率,在脑梗死组别中高于对照组(P<0.05)。同时,携带Ɛ3等位基因患者的低密度脂蛋白水平高于携带Ɛ2、Ɛ4等位基因的患者;进一步分析发现含Ɛ3等位基因的脑梗死患者NIHSS评分更高、卒中后认知障碍更严重(P<0.05)。结论 ApoE基因型为Ɛ3/4、等位基因Ɛ3、Ɛ4更易罹患大动脉粥样硬化型脑梗死,提示该基因型是脑梗死的易感基因,脑梗死后认知障碍患者Ɛ3等位基因的频率较高,可能是卒中后认知障碍的易感因素。
Objective To explore the relationship between ApoE gene polymorphisms and post-stroke cognitive impairment,the severity of large artery atherosclerotic cerebral infarction.Methods A case-control research study was conducted,gathering data from 100 individuals diagnosed with large artery atherosclerotic cerebral infarction according to the TOAST classification,who admitted to the Neurology Department of the Affiliated Hospital of Jiujiang University.Additionally,50 non-ischemic stroke patients,matched for gender and age,were included as the control group.The patients were assessed for ApoE genotype,blood lipid,NIHSS,and MMSE scale at 6 months post-stroke,and statistical methods were used to analyze their associations.Results Significant differences were observed in the ApoE 3/4 genotype frequency and Ɛ3、Ɛ4 allele frequency between patients with cerebral infarction and the control group,with a notably higher incidence of cerebral infarction in the former.Furthermore,patients carrying the Ɛ3 allele exhibited significantly higher LDL levels than those carrying Ɛ2 or Ɛ4.The analysis also revealed that patients with the Ɛ4 allele experienced higher NIHSS and severer post-stroke cognitive impairment.Conclusions The findings suggest that the ApoE genotype Ɛ3/4 and allele Ɛ3、Ɛ4 may predispose individuals to develop large atherosclerotic cerebral infarction,indicating a susceptibility gene for cerebral infarction.Additionally,the Ɛ3 allele was associated with a higher frequency of cognitive deficits after cerebral infarction,implying that it may be a predisposing factor for post-stroke cognitive impairment.
目的 探讨血清外泌体中糖蛋白 Ib 血小板亚基α(GP1BA)的表达水平与动脉粥样硬化的相关性。方法 选取福州市第二医院2022年1月—2023年1月收治的30例心电图提示ST-T改变及冠状动脉造影显示有AS斑块的患者为动脉粥样硬化组;30名健康志愿者为对照组。实时荧光定量(RT-qPCR)法和蛋白质印迹(WB)检测受试人员血清外泌体中GP1BA的表达量,ELISA法检测血清中肿瘤坏死因子α(TNF-α)、白细胞介素-1β(IL-1β)、干扰素-γ(IFN-γ)、高敏心肌肌钙蛋白(hs-cTnT)、血管性血友病因子(vWF)含量。采用Pearson相关系数分析血清外泌体中GP1BA的表达水平与TNF-α、IL-1β、IFN-γ、hs-cTnT、vWF的相关性。结果 动脉粥样硬化组血清外泌体中GP1BA的表达水平高于对照组,血清中TNF-α、IL-1β、IFN-γ、hs-cTnT、vWF含量升高(均P<0.05)。相关性分析发现GP1BA的表达水平与TNF-α、IL-1β、IFN-γ、hs-cTnT、vWF含量均呈较强正相关关系(均P<0.05)。结论 血清外泌体中GP1BA的表达水平与AS存在相关性,并可作为AS的潜在标志物。
目的 探讨大脑中动脉(MCA)粥样硬化斑块与脑梗死类型的相关性。方法 收集2018年1月—2020年12月的大脑中动脉粥样硬化患者178例,根据患者的临床表现、病史及诊断将患者分为脑梗死组(77例,按梗死部位分为深穿支梗死组、皮质梗死组和分水岭梗死组)和非脑梗死组(101例)。2组患者使用高分辨率核磁共振成像法(HRMRI)检查患者的双侧MCA粥样硬化斑块的特征,包括形态、信号强度及分布位置,从而统计分析粥样斑块特征与脑梗死类型之间的关系。结果 178例患者中77例为脑梗死患者。脑梗死组患者的强化率为55/77(71.4%),无脑梗死组患者的强化率为53/101(52.5%),相比差异有统计学意义(χ2=2.575,P=0.027)。其中脑梗死组中深穿支梗死组强化率为17/23(73.9%,χ2=8.707,P=0.021),皮质梗死组的强化率为13/19(68.4%,χ2=6.244,P=0.017),分水岭梗死组的强化率为25/35(71.4%,χ2=4.963,P=0.028),较非强化相比差异均有统计学意义。结论 大脑中动脉粥样硬化斑块的特征与脑梗死类型关系密切,斑块特征可反映斑块的稳定性,HRMRI对斑块稳定性的判断可预测脑梗死的发生及梗死位置。
Objective To explore the correlation between middle cerebral artery (MCA) atherosclerotic plaque and cerebral infarction patterns. Methods From January 2018 to December 2020, 178 patients with MCA atherosclerosis were divided into cerebral infarction group (77 cases, divided into deep perforating branch infarction group, cortical infarction group and watershed infarction group according to the infarct location) and non-cerebral infarction group (101 cases) according to their clinical manifestations, medical history and diagnosis.Two groups of patients underwent high-resolution magnetic resonance imaging (HRMRI) to examine the characteristics of bilateral MCA atherosclerotic plaques, including morphology, signal intensity and distribution location, to statistically analyze the relationship between the characteristics of atherosclerotic plaque and the patterns of cerebral infarction. Results Of 178 patients, 77 patients with cerebral infarction.The enhancement rate of the cerebral infarction group was 55/77 (71.4%), and that of the non-cerebral infarction group was 53/101 (52.5%), and difference between the two group had statistical significance(χ2=2.575, P=0.027). In the cerebral infarction group, the enhancement rate of the deep perforating branch infarction group was 17/23 (73.9%,χ2=8.707, P=0.021), that of the cortical infarction group was 13/19 (68.4%,χ2=6.244, P=0.017), and that of the watershed infarction group was 25/35 (71.4%,χ2=4.963, P=0.028), and the difference was statistically significant compared with the non-enhanced group. Conclusion The characteristics of MCA atherosclerotic plaque were closely related to the patterns of cerebral infarction,and the characteristics of plaque can reflect the stability of plaque.The judgment of plaque stability by HRMRI may predict the occurrence and paterrn of cerebral infarction.
目的 探讨复方丹参滴丸联合阿托伐他汀治疗对伴有颈动脉粥样硬化短暂性脑缺血发作患者脑循环动力的影响。方法 将2017年12月—2018年12我院收治入院的98例伴有颈动脉粥样硬化短暂性脑缺血发作患者为研究对象,随机分为观察组(49例,给予复方丹参滴丸联合阿托伐他汀治疗)和对照组(49例,给予阿托伐他汀治疗)。观察对比治疗前及治疗后2组患者每日短暂性脑缺血发作频率及持续时间,血脂水平、血流变指标、粥样硬化斑块及斑块面积。结果 治疗前,两组患者每日短暂性脑缺血发作频率、持续时间、各项血脂水平、脑循环动力学指标IMT 及斑块面积相比,差异无统计学意义(P>0.05);治疗后,2组患者每日短暂性脑缺血发作频率、持续时间、各项血脂水平、脑循环动力学指标IMT 及斑块面积相比均有所改善,其中观察组患者每日短暂性脑缺血发作频率、持续时间、各项血脂水平、脑循环动力学指标IMT 及斑块面积相比优于对照组,差异有统计学意义(P<0.05)。结论 在伴有颈动脉粥样硬化短暂性脑缺血发作患者中采用复方丹参滴丸联合阿托伐他汀治疗效果确切,可有效降低伴有颈动脉粥样硬化的短暂性脑缺血发作患者发作频率及持续时间,同时可有效调节患者血脂水平,改善对脑循环动力学指标,值得临床推广普及。
Objective To investigate the effect of compound Danshen dripping pills combined with atorvastatin on cerebral circulation dynamics in patients with transient ischemic attack accompanied by carotid atherosclerosis. Methods A total of 98 patients with transient ischemic attack with carotid atherosclerosis admitted to our hospital from December 2017 to December 2018 were randomly divided into observation group (49 cases, receiving compound danshen drop pill combined with atorvastatin) and control group (49 cases, receiving atorvastatin), to observe and compare the frequency and duration of transient ischemic attack, blood lipid level, hemorheological indexes, atherosclerotic plaque and plaque area of the two groups before and after treatment. Results Before treatment, there was no significant difference in frequency, duration, blood lipid levels, IMT and plaque area between the two groups (P>0.05). After treatment, 2 groups of patients with transient ischemic attack daily frequency, duration, the lipid levels and cerebral circulation dynamics index IMT and plaque area were improved. Compared with observation group of patients with transient ischemic attack daily frequency, duration, the lipid levels and cerebral circulation dynamics index IMT and plaque area were better than control group, the differences were statistical significance (P<0.05). Conclusion Patients in associated with carotid atherosclerosis with transient ischemic attack using compound danshen dropping pill with atorvastatin therapy have good effects. This may effectively reduce frequency and duration in patients with transient ischemic attack associated with carotid atherosclerosis, regulate blood lipid levels at the same time, and improve the dynamics of cerebral circulation index. It is worthy of clinical popularization.
近年来的研究已经报道证实了白细胞介素-33(IL-33)及其受体ST2可以保护心衰病人因机械应力过度牵拉所导致的心肌细胞肥大、心肌纤维化的发生以及可溶性ST2受体可作为潜在的心脏机械超负荷生物标志物。而对IL-33与受体ST2在动脉粥样硬化过程中发挥的作用少有涉及。本文主要探讨的是IL-33和ST2对抑制Th1/Th2漂移从而影响到动脉粥样硬化的进展以及血浆中可溶性ST2受体蛋白升高的意义。
Recent study has reported that interleukin-33(IL-33) and its receptor ST2 could prevent cardiomyocyte hypertrophy and exaggerated interstitial fibrosis which is because of the over harmful biomechanical force in patients with heart failure and soluble ST2 receptors is the potential biomarker of cardiac biomechanical overload. But few studies mentioned the sort of IL-33/ST2 complex plays a role in atherosclerosis. The purpose of this article is to explore the IL-33 and ST2 could reduce a Th1/Th2 shift. Consequently, it may improve the development of atherosclerosis and significance of soluble ST2 receptor increased in plasma.
目的 探讨载脂蛋白E(ApoE)基因多态性与卒中后认知障碍的相关性,即大动脉粥样硬化型脑梗塞的严重程度。方法 采用病例——对照研究的方法,收集九江学院附属医院神经内科的100例急性缺血性脑卒中且病因分型为大动脉粥样硬化型患者(脑梗死组)和50例性别、年龄匹配的非缺血性脑卒中患者(对照组)。检测患者的 ApoE 基因型、血脂、美国国立卫生院卒中量表(NIHSS)、卒中后6个月简易智力状态检查量表(MMSE)等,采用多因素方差分析等统计学方法分析他们之间的关联性。结果 ApoE 3/4基因型频率与Ɛ3、Ɛ4等位基因频率,在脑梗死组别中高于对照组(P<0.05)。同时,携带Ɛ3等位基因患者的低密度脂蛋白水平高于携带Ɛ2、Ɛ4等位基因的患者;进一步分析发现含Ɛ3等位基因的脑梗死患者NIHSS评分更高、卒中后认知障碍更严重(P<0.05)。结论 ApoE基因型为Ɛ3/4、等位基因Ɛ3、Ɛ4更易罹患大动脉粥样硬化型脑梗死,提示该基因型是脑梗死的易感基因,脑梗死后认知障碍患者Ɛ3等位基因的频率较高,可能是卒中后认知障碍的易感因素。
Objective To explore the relationship between ApoE gene polymorphisms and post-stroke cognitive impairment,the severity of large artery atherosclerotic cerebral infarction.Methods A case-control research study was conducted,gathering data from 100 individuals diagnosed with large artery atherosclerotic cerebral infarction according to the TOAST classification,who admitted to the Neurology Department of the Affiliated Hospital of Jiujiang University.Additionally,50 non-ischemic stroke patients,matched for gender and age,were included as the control group.The patients were assessed for ApoE genotype,blood lipid,NIHSS,and MMSE scale at 6 months post-stroke,and statistical methods were used to analyze their associations. Results Significant differences were observed in the ApoE 3/4 genotype frequency and Ɛ3、Ɛ4 allele frequency between patients with cerebral infarction and the control group,with a notably higher incidence of cerebral infarction in the former.Furthermore,patients carrying the Ɛ3 allele exhibited significantly higher LDL levels than those carrying Ɛ2 or Ɛ4.The analysis also revealed that patients with the Ɛ4 allele experienced higher NIHSS and severer post-stroke cognitive impairment.Conclusions The findings suggest that the ApoE genotype Ɛ3/4 and allele Ɛ3、Ɛ4 may predispose individuals to develop large atherosclerotic cerebral infarction,indicating a susceptibility gene for cerebral infarction.Additionally,the Ɛ3 allele was associated with a higher frequency of cognitive deficits after cerebral infarction,implying that it may be a predisposing factor for post-stroke cognitive impairment.