心肌纤维化是心力衰竭等心血管疾病演化过程中的关键性病理改变，该病的进展机制依赖巨噬细胞与成纤维细胞的相互调控。现有现代医学研究证实巨噬细胞可凭借M1、M2表型极化行为介导炎症反应与组织修复过程，成纤维细胞能够分化形成肌成纤维细胞并推动细胞外基质异常沉积，两类细胞可依托TGF-β/Smad、CSF-1/CSF-1R等信号通路构建相互调控的作用网络并介导心肌纤维化恶化。中医痰瘀互结病机理论指出痰浊与瘀血可相互滋生、交织阻滞，是各类慢性迁延性疾病的关键发病基础。本文以中医痰瘀互结理论为研究切入点，剖析该病机理论与巨噬细胞、成纤维细胞交互作用的内在关联，整合现代医学关于两种细胞交互作用的现有研究成果，深入分析细胞互作在心肌纤维化发病过程中的协同机制与病理关联，旨在为心肌纤维化的中西医协同防治提供理论依据，为相关动物实验及临床应用研究筑牢研究基础。

Myocardial fibrosis is a key pathological change in the progression of cardiovascular diseases such as heart failure. The progression mechanism of this disease relies on the reciprocal regulation between macrophages and fibroblasts. Current modern medical research has confirmed that macrophages can mediate inflammatory responses and tissue repair processes through M1 and M2 phenotypic polarization behaviors, and fibroblasts can differentiate into myofibroblasts and promote abnormal extracellular matrix deposition. The two types of cells can construct a reciprocal regulatory network through signaling pathways such as TGF-β/Smad and CSF-1/CSF-1R, thereby mediating the deterioration of myocardial fibrosis. The theory of phlegm and blood stasis intermingling in traditional Chinese medicine suggests that phlegm turbidity and blood stasis can mutually generate and interweave to cause obstruction, serving as a key pathological basis for various chronic and persistent diseases. This article takes the traditional Chinese medicine theory of phlegmblood stasis intermingling as a research entry point, analyzes the intrinsic relationship between this pathological theory and the interaction of macrophages and fibroblasts, integrates existing modern medical research findings on the interaction between the two cell types, and deeply analyzes the synergistic mechanisms and pathological correlations of cellcell interactions in the pathogenesis of myocardial fibrosis. The aim is to provide a theoretical basis for the integrated traditional Chinese and Western medicine prevention and treatment of myocardial fibrosis, and also to lay a solid research foundation for related animal experiments and clinical application studies.

心肌纤维化是心力衰竭等心血管疾病演化过程中的关键性病理改变，该病的进展机制依赖巨噬细胞与成纤维细胞的相互调控。现有现代医学研究证实巨噬细胞可凭借M1、M2表型极化行为介导炎症反应与组织修复过程，成纤维细胞能够分化形成肌成纤维细胞并推动细胞外基质异常沉积，两类细胞可依托TGF-β/Smad、CSF-1/CSF-1R等信号通路构建相互调控的作用网络并介导心肌纤维化恶化。中医痰瘀互结病机理论指出痰浊与瘀血可相互滋生、交织阻滞，是各类慢性迁延性疾病的关键发病基础。本文以中医痰瘀互结理论为研究切入点，剖析该病机理论与巨噬细胞、成纤维细胞交互作用的内在关联，整合现代医学关于两种细胞交互作用的现有研究成果，深入分析细胞互作在心肌纤维化发病过程中的协同机制与病理关联，旨在为心肌纤维化的中西医协同防治提供理论依据，为相关动物实验及临床应用研究筑牢研究基础。

Myocardial fibrosis is a key pathological change in the progression of cardiovascular diseases such as heart failure. The progression mechanism of this disease relies on the reciprocal regulation between macrophages and fibroblasts. Current modern medical research has confirmed that macrophages can mediate inflammatory responses and tissue repair processes through M1 and M2 phenotypic polarization behaviors, and fibroblasts can differentiate into myofibroblasts and promote abnormal extracellular matrix deposition. The two types of cells can construct a reciprocal regulatory network through signaling pathways such as TGF-β/Smad and CSF-1/CSF-1R, thereby mediating the deterioration of myocardial fibrosis. The theory of phlegm and blood stasis intermingling in traditional Chinese medicine suggests that phlegm turbidity and blood stasis can mutually generate and interweave to cause obstruction, serving as a key pathological basis for various chronic and persistent diseases. This article takes the traditional Chinese medicine theory of phlegmblood stasis intermingling as a research entry point, analyzes the intrinsic relationship between this pathological theory and the interaction of macrophages and fibroblasts, integrates existing modern medical research findings on the interaction between the two cell types, and deeply analyzes the synergistic mechanisms and pathological correlations of cellcell interactions in the pathogenesis of myocardial fibrosis. The aim is to provide a theoretical basis for the integrated traditional Chinese and Western medicine prevention and treatment of myocardial fibrosis, and also to lay a solid research foundation for related animal experiments and clinical application studies.

       目的 探索α-突触核蛋白（α-Syn）干预对人单核细胞白血病细胞系（THP-1）巨噬细胞源性泡沫细胞的影响。方法 通过佛波酯（PMA）和氧化型低密度脂蛋白（ox-LDL）构建THP-1巨噬细胞源性泡沫细胞模型,使用不同浓度（33、66、100、133 nmol/L）α-Syn处理泡沫细胞,随后检测细胞胆固醇含量和炎症因子白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）及白细胞介素-8（IL-8）的mRNA表达以及核因子κB（NF-κB）和凝集素样氧化低密度脂蛋白受体-1（LOX-1）的蛋白表达变化。结果 高剂量（100和133 nmol/L）α-Syn处理可以减少THP-1巨噬细胞源性泡沫细胞内胆固醇的含量（P<0.05）,并且减少IL-1β、IL-6和IL-8的mRNA表达（P<0.05）。进一步发现（100 nmol/L和133 nmol/L）α-Syn可以降低THP-1巨噬细胞源性泡沫细胞p-NF-κB和LOX-1的蛋白表达（P<0.05）。结论 α-Syn可以降低THP-1源性巨噬细胞泡沫细胞胆固醇蓄积和炎症反应,可能是通过下调p-NF-κB和LOX-1蛋白表达。

      Objective To explore the effects of α-synuclein（α-Syn）intervention on human monocytic leukemia cell（THP-1）macrophage-derived foam cells．Methods The THP-1 macrophage-derived foam cell model was constructed by phorbol 12-myristate 13-acetate（PMA）and oxidized low-density lipoprotein（ox-LDL）．Foam cells were treated with different concentrations（33, 66, 100, and 133 nmol/L）of α-Syn, and the cellular cholesterol contents, as well as the mRNA expression of IL-1β、IL-6 and IL-8 were detected．Subsequently,alternation in protein expression of NF-κB and LOX-1 was measured．Results High-dose（100 and 133nmol/L）α-Syn treatment significantly reduced the levels of intracellular cholesterol in THP-1-derived macrophage foam cells（P<0.05）and decreased the mRNA expression of IL-1β、IL-6 and IL-8（P<0.05）．It was further found that（100 nmol/L and 133 nmol/L）α-Syn decreased the protein expression of p-NF-κB and LOX-1 in THP-1 macrophage-derived foam cells（P<0.05）．Conclusions The results of the present study suggest that α-Syn reduces cholesterol accumulation and inflammatory response in THP-1-derived macrophage foam cells, possibly by down-regulating p-NF-κB and LOX-1 protein expression．

肿瘤相关巨噬细胞（TAMs）是肿瘤微环境中最丰富的免疫细胞之一,M2-TAMs在肿瘤发生、发展、转移和治疗过程中发挥重要作用,被认为是肿瘤治疗中的重要靶点。已有的研究表明,通过将促肿瘤的M2-TAMs重编程为促炎的M1-TAMs可实现抑制肿瘤生长和转移。本综述在介绍TAMs与肿瘤治疗相关背景的基础上,重点关注纳米药物重编程TAMs增强抗肿瘤的研究进展。本文将从TAMs靶向递送各种活性物质进行重编程TAMs和纳米药物介导的异常肿瘤微环境调节的间接重编程TAMs两种方式,综述近年来基于纳米药物递送系统的调控策略及典型例子。

Tumor associated macrophages（TAMs）is one of the most abundant immune cells in the tumor microenvironment．M2-TAMs play an important role in tumor genesis,progression,metastasis and treatment,and is additionally a very important target in tumor therapy．Previous studies have shown that inhibition of tumor growth and metastasis can be achieved by reprogramming M2-TAMs to M1-TAMs．On the basis,this review focuses on the analysis progress of nano-drug reprogramming TAMs to boost anti-tumor．In this paper,we reviewed two methods of reprogramming TAMs for targeted delivery of various active substances and indirect reprogramming TAMs for abnormal tumor microenvironment regulation mediated by nanomedicine．The regulatory strategies and typical samples of nanomedicine delivery systems in recent years were summarized.

目的 探讨磷酸二酯酶4抑制剂对人肺泡巨噬细胞(AM)吞噬非生物性颗粒及革兰阳性菌、阴性菌能力的影响。方法 使用Ficolll-Hypaque密度梯度法将外周血单核细胞分离的静脉血,在含有2 ng/m GM-CSF的培养液中经12天诱导培养成AM替代细胞模型—单核细胞源性巨噬细胞(MDM)。用酶标仪检测MDM经磷酸二酯酶4抑制剂Rolipram预处理过夜(16~18 h)后吞噬荧光标记的非生物颗粒Beads和热灭活的流感嗜血杆菌(H.influenzae)、金黄色葡萄球菌(S.aureus)量的改变,另使用MTT法检测细胞活性。结果 成功建立的MDM细胞模型对Beads和细菌的吞噬呈时效关。Rolipram在实验浓度(10^~8~10^-5 M)下对MDM吞噬Beads、H.influenzae和S.aureus能力无明显促进或抑制作用,也不影响MDM的活性。结论 磷酸二酯酶4抑制剂不会因升高巨噬细胞内cAMP水平而影响其吞噬非生物颗粒和细菌的能力。

Objective To investigate the influence of phosphodiesterases 4 inhibitor on the phagocytosis of non-biological particles and gram-positive bacteria, gram-negative bacteria by human alveolar macrophages. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood from 12 healthy volunteers using Ficoll-Hypaque density gradients. Monocytes were incubated with media containing 2 ng/ml GM-CSF for 12d to allow full differentiation into macrophage (MDM), a functionally equivalent model of human AM. MDM were pretreated with Rolipram overnight (16-18h),phagocytosis of fluorescent labeled beads and H.influenzae,S.aureus by MDM was measured using a fluostar optima fluorimeter. Cell viability was assay with MTT. Results MDM phagocytosis of beads and bacteria was a time-dependant process. Rolipram in the concentration of 10^-8-10^-5M didn't inhibit or promote phagocytosis of beads and bacteria by MDM, and didn't affect the cell viability. Conclusion Phosphodiesterases 4 inhibitor would not affect the human macrophage phagocytic capacity of non-biological particles and bacteria associated with enhanced intracellular cAMP level.