巨噬细胞极化在肺部疾病中的作用机制及中药的干预

巨噬细胞作为机体重要的免疫细胞,是参与维持肺内微环境稳态的关键因素,由于其高度的可塑性,可在不同的条件下极化为不同的亚型：经典活化巨噬细胞M1和选择性活化巨噬细胞M2,两者分别具有促炎和抗炎作用。M1/M2表型与肺部疾病的发生发展密切相关,在巨噬细胞极化过程中涉及的多种信息分子和细胞因子在各种肺部疾病中均有重要的调控表型的作用,且在不同疾病中表型的转换也存在明显差异。该文主要通过综述巨噬细胞极化生物学特性,探讨巨噬细胞极化在支气管哮喘、慢性阻塞性肺疾病、急性肺损伤、肺纤维化等肺部疾病中的作用特点和以调控巨噬细胞极化为靶点的中药单体及中药复方对相关疾病的研究进展,旨在挖掘巨噬细胞极化在调控肺部炎症方面的潜力,为相关临床研究提供新思路。     

滑膜巨噬细胞影响骨性关节炎的研究进展

骨性关节炎(osteoarthritis, OA)是一种慢性、退行性关节病变,是临床上最常见的关节疾病,又称退行性关节炎,主要特点是关节软骨退变和骨赘形成,最终导致关节畸形、运动能力丧失,严重影响老年人生活质量的重要疾病。虽然OA以关节软骨退变为主要病理表现，但其病理变化又决不仅限于软骨局部，而是影响关节内所有组织的全关节疾病。骨细胞，软骨细胞和滑膜细胞之间通过释放可溶性介质及机械信号完成进行细胞间通信。越来越多的研究发现，滑膜炎症在OA的发生和发展中发挥重要作用，而关节炎滑膜中以巨噬细胞为主体的混合性炎症浸润则是关键。滑膜巨噬细胞被微环境刺激所激活，分化为促炎因子的M1亚型和产生抗炎因子的M2亚型两种功能极化状态，这一过程会产生一系列的炎症因子间动态变化。由于巨噬细胞的动态平衡在疾病发展过程中的重要性，巨噬细胞已经成为OA病理机制和治疗策略的研究热点。本综述将回顾和总结涉及滑膜炎与OA的研究，这些研究强烈提示滑膜炎和活化的滑膜巨噬细胞在促进OA病理学中的重要性。特别是，我们将概述滑膜巨噬细胞在促进OA炎症和破坏性反应中的作用以及针对巨噬细胞或巨噬细胞产生的细胞因子作为该疾病治疗策略的潜在作用。     

巨噬细胞激活与极化在心肌纤维化的作用及中医药干预

心肌纤维化（MF）是多种心脏疾病的常见病理表现,由于心肌细胞的不可再生性,MF的发生代表心肌出现不可逆性的损伤。以往的研究认为,成纤维细胞介导的胶原沉积是心肌纤维化的主要机制。最新的研究发现,心脏本身存在免疫调控机制,巨噬细胞激活/极化在MF中占有重要地位。随着中医药研究的不断深入,学者们发现中药可通过调控肾素-血管紧张素-醛固酮系统（RAAS）系统、调节炎症进程、修复细胞外基质、管理氧化应激、维护自噬平衡等方面干预MF,而这一过程与巨噬细胞的激活及M1/M2型极化密切相关。在整个MF过程中,巨噬细胞活化是有益的,但不可过度,否则将变为有害。在MF早期,适当的M1型巨噬细胞极化有利于激活免疫,清除有害物质;在MF中后期,适当的M2型巨噬细胞极化有利于重塑受损的心肌。若巨噬细胞活化过度/不足,或M1/M2型巨噬细胞极化的平衡被打破,则效应由挽救变为破坏。具有调控巨噬细胞活化/极化的中药多具有益气养阴,理气活血的功效,但也不乏清热燥湿解毒之品。因此,MF的发生可能为气阴不足、湿热蕴毒、气滞血瘀所致。通过总结巨噬细胞激活/极化在MF中涉及的生物学过程,阐述中医药从不同角度调控巨噬细胞激活及M1/M2型极化改善MF的研究进展,以期为中医药治疗MF提供借鉴。     

巨噬细胞极化与动脉粥样硬化的研究进展

作为一种主要影响大中动脉的慢性炎症性疾病,动脉粥样硬化是心血管疾病的主要病因。巨噬细胞极化在动脉粥样硬化形成中发挥了重要作用。巨噬细胞可根据周围微环境的变化极化为促炎的M1型和抗炎的M2型,研究表明,通过调控巨噬细胞的极化可以有效控制动脉粥样硬化的进展。总结了近年来巨噬细胞极化在动脉粥样硬化形成中的作用,及药物调控巨噬细胞极化防治动脉粥样硬化的研究进展,以期为动脉粥样硬化的形成机制及临床防治研究提供新思路。     

吴茱萸碱抑制M2型巨噬细胞功能的机制研究

目的：吴茱萸碱是中药吴茱萸重要生物碱成分之一,其具有明显的抗炎作用,但具体机制不清。研究显示瞬时受体电位香草醛亚型1受体（Transient Receptor Potential Vanilloid Type 1 Channel,TRPV1）对炎症反应具有明显的抑制作用,而吴茱萸碱可激活TRPV1受体。本研究以人单核细胞（THP-1）培养模型,探明吴茱萸碱对M2型巨噬细胞功能的影响及TRPV1受体参与该过程中的作用,从而阐明吴茱萸碱抑制炎症反应的分子生物机制。方法：在THP-1细胞培养模型上,观察吴茱萸碱对白介素-4（Interleukin-4,IL-4）诱导的M2型巨噬细胞功能的影响,以及特异性TRPV1受体拮抗剂Capsazepine（CAPZ）对该过程的影响,并分别利用ELISA、荧光定量PCR和western blot确定M2型巨噬细胞功能指标,其中包括TGF-β1的产生、Arginase-1和Mannose Receptor mRNA和蛋白的表达。结果：本研究发现吴茱萸碱明显抑制IL-4诱导的M2型巨噬细胞功能亚型,其主要表现为TGF-β1分泌产生下降（P<0.05）,同时伴有Arginase-1和Mannose Receptor mRNA和蛋白表达的降低（P<0.05）,以上结果可被特异性TRPV1受体拮抗剂CAPZ所阻断（P<0.05）。结论：本研究显示吴茱萸碱通过激活TRPV1受体抑制M2型巨噬细胞功能反应,从而实现其抑制炎症反应的作用。     

基于巨噬细胞亚型分化探讨中医药防治动脉粥样硬化的研究进展

动脉粥样硬化是心脑血管疾病的重要病理基础,其发病机制是血管生物学领域的研究热点。炎症诱发学说在近几年的研究中日趋深入和成熟,M1型和M2型巨噬细胞分别通过发挥促炎与抑炎作用,参与并影响动脉粥样硬化的发展进程。在治疗动脉粥样硬化方面,中药复方及有效成分对巨噬细胞M1、M2亚型间的转化具有多靶点协同作用,故主要从巨噬细胞极化为M1、M2亚型的诱发因子、激活途径、干预靶点等方面探讨中医药抗动脉粥样硬化的可能机制。     

基于阴阳学说探讨巨噬细胞极化在心力衰竭炎症中的作用

炎症是心力衰竭(以下简称"心衰")的关键致病特征,其过表达可致心肌肥大、凋亡及纤维化,加重心衰的进程。巨噬细胞是人体重要的免疫细胞,具有高度异质性,参与炎症反应及维持心脏稳态。巨噬细胞极化是一个动态过程,在不同微环境的刺激下,巨噬细胞可极化2个亚群:经典激活的M1型和替代激活的M2型,两者相互拮抗。当巨噬细胞极化为促炎表型M1为主时,启动炎症反应;以抗炎表型M2为主时,发挥抑制心衰炎症、修复组织作用。同时,在心衰发展的不同阶段,M1和M2之间可相互转化,这与中医学说的阴阳制约、平衡和转化内涵相似。基于此,笔者拟通过阴阳理论来阐明M1与M2型巨噬细胞之间的关系,提出临床防治心衰应重视微观和宏观的炎症反应,调控巨噬细胞极化,使"抗炎"和"促炎"达到平衡,这与中医理论中调节机体阴阳平衡相一致,可为心衰的中医药治疗提供新靶点和新方向。     

益气养阴逐瘀方对LPS诱导的RAW 264.7细胞炎症模型体外抗炎活性的影响

目的:研究益气养阴逐瘀方对脂多糖(LPS)诱导的小鼠单核巨噬细胞系RAW 264. 7细胞炎症模型相关细胞因子表达及经典活化(M1)/选择性活化(M2)炎症表型转化的影响。方法:运用噻唑蓝(MTT)比色法检测不同给药浓度的益气养阴逐瘀方对RAW 264. 7细胞增殖情况的影响;利用LPS诱导RAW 264. 7细胞,构建体外炎症模型,采用格里斯试剂法(Griess)检测细胞上清液中一氧化氮(NO)的分泌量;酶联免疫吸附测定法(ELISA)检测细胞上清中M1/M2型相关炎症因子肿瘤坏死因子-α(TNF-α),白细胞介素-6(IL-6),白细胞介素-1β(IL~(-1)β),一氧化氮合酶(i NOS),白细胞介素-10(IL~(-1)0),转化生长因子-β(TGF-β),精氨酸-1(Arg-1)的表达量;实时荧光定量PCR(Real-time PCR)检测M1型巨噬细胞标志基因TNF-α,IL-6,IL~(-1)β,i NOS和M2型巨噬细胞标志基因IL~(-1)0,TGF-β,Arg-1 mRNA的表达;蛋白免疫印迹法(Western blot)检测细胞内相关蛋白TNF-α,IL-6,IL~(-1)β,i NOS的表达。结果:MTT比色法显示,与空白组比较,益气养阴逐瘀方2. 0 g·L~(-1)及以下时对细胞增殖无明显影响。Griess法显示,与空白组相比,LPS组NO释放量显著上调(P 0. 01);与LPS组相比,各给药组NO释放量均显著下调(P 0. 01)。ELISA显示,与空白组相比,LPS组M1/M2型巨噬细胞相关炎症因子表达均显著上调(P 0. 01);与LPS组相比,益气养阴逐瘀方各给药组可明显下调M1型巨噬细胞促炎症因子表达(P 0. 01),对M2型巨噬细胞抗炎症因子无影响。Real-time PCR显示,与空白组相比,LPS组M1/M2型巨噬细胞相关mRNA表达显著上调(P 0. 01);与LPS组相比,益气养阴逐瘀方各给药组可明显下调M1型巨噬细胞促炎症因子基因表达(P 0. 05,P 0. 01),对M2型mRNA表达无影响。Western blot显示,与空白组比较,LPS组TNF-α,IL-6,IL~(-1)β,i NOS蛋白的表达显著上调(P 0. 01);与LPS组相比,益气养阴逐瘀方各给药组TNF-α,IL-6,IL~(-1)β,i NOS蛋白的表达均下调,且于2. 0 g·L~(-1)下调最显著(P 0. 01)。结论:益气养阴逐瘀方可以有效抑制LPS诱导的RAW 264. 7细胞炎症。其诱导已经分化的促炎亚型M1型巨噬细胞向抗炎亚型M2型巨噬细胞转化不明显,其抗炎机制可能与通过抑制巨噬细胞向M1亚型方向极化从而发挥免疫调节作用,以减少NO,TNF-α,IL-6等相关炎症因子分泌相关。     

中药提取物调控巨噬细胞极化研究进展

巨噬细胞是一类具有异质性和可塑性的免疫细胞,在不同细胞因子和趋化因子作用下可极化为M1和M2两种不同的表型,M2型又分为M2a、M2b、M2c亚群。M1型巨噬细胞能产生促炎因子和介质,导致炎症的发生;而M2型巨噬细胞则具有抗炎作用,但其中的肿瘤相关巨噬细胞有促进肿瘤进展的不利作用。越来越多研究表明,巨噬细胞极化在炎症相关疾病和肿瘤的进程中起关键作用,调节巨噬细胞极化逐渐成为这些疾病治疗的一种新策略。大量研究表明,中药是巨噬细胞极化调控化合物的重要来源。本文综述近年来中药提取物调控巨噬细胞M1和M2型极化研究进展。     

肥胖慢性炎症中医药治疗的潜在靶点：巨噬细胞极化

肥胖被认定为一种全身的慢性低度炎症状态，是糖尿病、高血压病及恶性肿瘤发生的关键危险因素，已成为亟待解决的全球性健康负担。脂肪组织巨噬细胞是脂肪免疫稳态及炎症反应的主要参与者，在不同状态下可极化为促炎M1表型及抑炎M2表型，肥胖个体脂肪组织存在巨噬细胞的异常极化，导致M1/M2表型动态平衡紊乱，产生病理性炎症反应。因此，恢复M1/M2巨噬细胞极化的平衡是治疗肥胖慢性炎症的重要潜在靶点。研究证实，中医药可通过调控巨噬细胞极化，对肥胖产生积极的疗效。基于现有证据，该文从巨噬细胞极化角度切入，系统综述中医药改善肥胖慢性炎症的潜在机制，以期为肥胖慢性炎症的中医药临床诊治提供证据，为相关科研设计及中药新药研发提供新思路。     

二妙散对大鼠骨髓来源的巨噬细胞M1/M2极化的影响

目的:探索二妙散(EMS)对脂多糖(LPS)+干扰素(IFN)-γ诱导大鼠骨髓来源巨噬细胞(Macrophage)M1极化及白细胞介素(IL)-4+IL-13诱导M2极化的影响。方法:体外提取大鼠骨髓来源的单核细胞,加巨噬细胞集落刺激因子(M-CSF),诱导成巨噬细胞(F4/80标记),加入LPS+IFN-γ,诱导其向M1型巨噬细胞极化;加入IL-4和IL-13,诱导其向M2型巨噬细胞极化;加入不同浓度二妙散(0.2,0.4,0.8 g·L^-1)作用后,采用免疫荧光分别检测M1(CD68及iNOS标记)及M2(CD206及Arginase标记)表型,检测二妙散对大鼠骨髓来源的巨噬细胞M1/M2极化的影响。结果:与空白组比较,LPS+IFN-γ能显著增加M1的极化(P<0.01),IL-4+IL-13能显著增加M2的极化(P<0.01);与LPS+IFN-γ/IL-4+IL-13组比较,二妙散(0.2,0.4,0.8 g·L^-1)作用24 h对LPS+IFN-γ诱导的M1极化具有明显抑制作用(P<0.05),对IL-4+IL-13诱导的M2极化没有明显影响。结论:二妙散可抑制LPS+IFN-γ诱导的M1极化,而对IL-4+IL-13诱导的M2极化没有影响。     

Triterpenoids‐Enriched Extract from the Aerial Parts of Salvia miltiorrhiza Regulates Macrophage Polarization and Ameliorates Insulin Resistance in High‐Fat Fed Mice

Adipose tissue inflammation and macrophage polarization are tightly associated with the development of obesity‐associated insulin resistance. Our previous studies have demonstrated the triterpenoids‐enriched extract from the aerial parts of Salvia miltiorrhiza (TTE) could significantly improve atherosclerosis in LDLR^?/? mice. However, its molecular mechanisms of TTE ameliorating insulin resistance remain unclear. In the present study, obesity model with insulin resistance induced by feeding high‐fat diet (HFD) was established. Dietary TTE attenuated hyperlipidemia, improved glucose intolerance in mice and mediated the activation of IRS‐1/PI3K/Akt insulin signaling pathway. Meanwhile, dietary TTE also attenuated macrophage infiltrations into adipose tissue and modified the phenotype ratio of M1/M2 macrophages. Furthermore, our results showed that TTE regulated the polarization of macrophages partly via adenosine monophosphate‐activated kinase (AMPK). Taken together, these findings suggested that TTE has a potential clinical utility in improving insulin resistance. Its mechanisms might be contributed to its beneficial effects on macrophage polarization via AMPK. Copyright © 2016 John Wiley & Sons, Ltd.     

M1/M2型肺泡巨噬细胞亚群在新型冠状病毒肺炎中的作用及中医药调控机制研究进展

新型冠状病毒肺炎(COVID-19)死亡患者的病理解剖结果显示肺部过度的炎症反应是诱发急性肺损伤或急性呼吸窘迫综合征等并发症的重要原因之一,调节过度的免疫应答对治疗该病有重要的意义。肺泡巨噬细胞具有高度的异质性和可塑性,在机体感染早期和后期,M1/M2型肺泡巨噬细胞亚群平衡及功能的动态变化对肺部炎性反应具有显著的影响。本文综述巨噬细胞的分型及功能,探讨巨噬细胞在新冠肺炎不同阶段病理过程的作用机制以及中药治疗的药效机制,为中医药治疗新型冠状病毒肺炎以及基于调控巨噬细胞极化的药物研发上提供思路。     

肿瘤中巨噬细胞表型极化的调控机制及中药干预的研究进展

巨噬细胞具有异质性和多样性,可随所在的器官微环境和生理病理条件极化成不同的表型.M1经典性激活和M2替代性激活是巨噬细胞表型极端化后的2个主要亚群,分别表达不同的表面受体,分泌不同的细胞因子、趋化因子,受转录和表观遗传水平各个信号通路的调控,并在肿瘤发展中行使不同的功能,而中药有可能通过调控巨噬细胞表型极化而改善微环境.目前对于巨噬细胞极化途径产生的特异性标志和极化的分子机制尚在研究进程中,该文就目前国内外对于巨噬细胞表型极化和调控机制的研究进展进行综述及对中药干预进行展望.     

Extracts of Crinum latifolium inhibit the cell viability of mouse lymph oma cell line EL4 and induce activation of anti-tumour activity of macrophages in vitro

Ethnopharmacological relevance

Crinum latifolium L. (CL) leaf extracts have been traditionally used in Vietnam and are now used all over the world for the treatment of prostate cancer. However, the precise cellular mechanisms of the action of CL extracts remain unclear.

Aim of the study

To examine the effects of CL samples on the anti-tumour activity of peritoneal murine macrophages.

Materials and methods

The properties of three extracts (aqueous, flavonoid, alkaloid), one fraction (alkaloid), and one pure compound (6-hydroxycrinamidine) obtained from CL, were studied (i) for redox capacities (DPPH and bleaching beta-carotene assays), (ii) on murine peritoneal macrophages (MTT assay) and on lymphoma EL4-luc2 cells (luciferine assay) for cytotoxicity, (iii) on macrophage polarization (production of ROS and gene expression by PCR), and (iv) on the tumoricidal functions of murine peritoneal macrophages (lymphoma cytotoxicity by co-culture with syngeneic macrophages).

Results

The total flavonoid extract with a high antioxidant activity (IC₅₀=107.36 mg/L, DPPH assay) showed an inhibitory action on cancer cells. Alkaloid extracts inhibited the proliferation of lymphoma cells either by directly acting on tumour cells or by activating of the tumoricidal functions of syngeneic macrophages. The aqueous extract induced mRNA expression of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin 6 (IL-6) indicating differentiation of macrophages into pro-inflammatory M1 polarized macrophages. The total flavonoid, alkaloid extracts and an alkaloid fraction induced the expression of the formyl peptide receptor (FPR) on the surface of the polarized macrophages that could lead to the activation of macrophages towards the M1 phenotype. Aqueous and flavonoid extracts enhanced NADPH quinine oxido-reductase 1 (NQO1) mRNA expression in polarized macrophages which could play an important role in cancer chemoprevention. All the samples studied were non-toxic to normal living cells and the pure alkaloid tested, 6-hydroxycrinamidine, was not active in any of the models investigated.

Conclusions

Our results indicate that CL extracts and alkaloid fraction (but not pure 6-hydroxycrinamidine) inhibit the proliferation of lymphoma cells in multiple pathways. Our results are in accordance with traditional usage and encourage further studies and in vivo assays.     

Tanshinone IIA prevents acute lung injury by regulating macrophage polarization

ObjectiveAcute lung injury (ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone IIA (Tan-IIA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-IIA on ALI.MethodsA murine model of lipopolysaccharide (LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-IIA were investigated using in vivo and in vitro ALI models. Tan-IIA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-IIA function.ResultsThe cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-IIA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-IIA treatment. An in vitro assay also confirmed that including the Tan-IIA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-IIA inhibited activations of the nuclear factor-κB and hypoxia-inducible factor pathways. Including Tan-IIA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization.ConclusionThis study found that while an LPS-induced cytokine storm exacerbated ALI, including Tan-IIA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization.     

Quercetin protects against cisplatin‐induced acute kidney injury by inhibiting Mincle/Syk/NF‐κB signaling maintained macrophage inflammation

Acute kidney injury (AKI) with high incidence and mortality is the main cause of chronic kidney disease. Previous studies have indicated that quercetin, an abundant flavonoid in plants, exhibited renoprotective role in AKI. However, the underlying mechanism is largely unknown. In this study, we try to explore whether quercetin protects against AKI by inhibiting macrophage inflammation via regulation of Mincle/Syk/NF‐κB signaling. The results demonstrated that quercetin can significantly inhibit expression and secretion of IL‐1β, IL‐6, and TNF‐α in LPS‐induced bone marrow‐derived macrophages (BMDMs) and reduce activity of Mincle/Syk/NF‐κB signaling in vitro. We also found that quercetin can strongly reduce the concentration of serum creatinine, BUN, IL‐1β, IL‐6, and TNF‐α in cisplatin‐induced AKI model. Furthermore, quercetin down‐regulated protein levels of Mincle, phosphorylated Syk and NF‐κB in kidney macrophages of AKI, as well as inhibited M1, up‐regulated M2 macrophage activity. Notably, the down‐regulation of LPS‐induced inflammation by quercetin was reversed after adding TDB (an agonist of Mincle) in BMDMs, suggesting that quercetin suppresses macrophage inflammation may mainly through inhibiting Mincle and its downstream signaling. In summary, these findings clarified a new mechanism of quercetin improving AKI‐induced kidney inflammation and injury, which provides a new drug option for the clinical treatment of AKI.     

Ginsenoside RG1-induced mesenchymal stem cells alleviate diabetic cardiomyopathy through secreting exosomal circNOTCH1 to promote macrophage M2 polarization

Diabetic cardiomyopathy (DCM) is a cardiac complication resulting from long-term uncontrolled diabetes, characterized by myocardial fibrosis and abnormal cardiac function. This study aimed at investigating the potential of ginsenoside RG1 (RG1)-induced mesenchymal stem cells (MSCs) in alleviating DCM. A DCM mouse model was constructed, and the effects of RG1-induced MSCs on myocardial function and fibrosis in diabetic mice were evaluated. RG1-induced MSCs were cocultured with high glucose-treated fibroblasts for subsequent functional and mechanism assays. It was discovered that RG1-induced MSCs secrete exosomes that induce macrophage M2 polarization. Mechanistically, exosomes derived from RG1-induced MSCs transferred circNOTCH1 into macrophages, activating the NOTCH signaling pathway. A competing endogenous RNA (ceRNA) regulatory axis consisting of circNOTCH1, miR-495-3p, and NOTCH1 was found to contribute to DCM alleviation.. This study unveiled that exosomal circNOTCH1 secreted by RG1-induced MSCs can alleviate DCM by activating the NOTCH signaling pathway to induce macrophage M2 polarization. This finding may contribute to the development of new therapeutic approaches for DCM.     

益气扶正方通过调控肿瘤相关巨噬细胞极化抗肺癌转移的实验研究

目的 阐释益气扶正方调控肿瘤相关巨噬细胞表型转化的作用及机制.方法 ①建立体外诱导的M2型肿瘤相关巨噬细胞模型,采用CCK-8实验确定益气扶正方的给药浓度,流式技术鉴定给药后各组M1和M2型肿瘤相关巨噬细胞的表达情况,利用RT-PCR技术检测给药后各组肿瘤相关巨噬细胞中CCL2、AMPK、mTOR mRNA表达水平,W...