中药复方防治急性肺损伤的作用机制研究进展

急性肺损伤(acute lung injury,ALI)是各种直接或间接因素导致的肺泡上皮细胞及毛细血管内皮细胞损伤,能造成弥漫性肺间质及肺泡水肿,由其导致的急性低氧性呼吸功能不全,是临床上常见的危重病症,至今尚缺乏有效的治疗药物.中药复方在防治肺损伤方面日益显示其优势,其作用机制研究也不断深入.作者分别从抑制炎性反应、调节免疫功能、抗氧化、调节凝血和纤溶系统的异常、上调水通道蛋白及减轻肺纤维化等6方面,对近3年来相关研究进展进行综述,并总结了中医治则与现代药理机制之间的关联,以期为研制防治ALI的创新药物提供一定依据和线索.     

从虚论治肝纤维化相关方剂的现代药理作用研究进展

肝纤维化表现为炎症细胞浸润、肝星状细胞激活、细胞外基质沉积及瘢痕组织形成，是各类慢性肝病向各类终末期肝病转变的关键病理过程。近年来，中医药被证明在防治肝纤维化方面成果突出，中医学对肝纤维化具有极富特色的诊疗理念，认为肝纤维化基本证候病机中“虚损”为其根本，并集中表现为气虚络瘀、肝郁脾虚和肝肾阴虚等证型，通过对以上3种常见肝纤维化证型总结相应常用效验方剂的临床及药理学研究进展，归纳其调控肝星状细胞命运、调节胆汁酸代谢、促进细胞外基质降解、抑制肝窦内皮血管化等潜在作用机制，为临床防治肝纤维化提供新思路。     

基于VEGFR,FGFR探讨中药方剂对COVID-19后遗症肺纤维化的干预作用

自2020年2月以来,随着疫情防控力度的加强,大批新型冠状病毒肺炎(COVID-19)患者治愈出院。肺纤维化是冠状病毒肺炎的后遗症之一,其不仅引起呼吸困难和肺功能指标的恶化,还具有死亡率高、预后不良的特点,严重影响患者的生活质量。血管内皮生长因子受体(vascular endothelial growth factor receptor,VEGFR)、成纤维生长因子受体(fibroblast growth factor receptor,FGFR)通过介导参与肺纤维化进程的信号转导通路,抑制成纤维细胞增殖、活化与迁移,影响肺纤维的发生发展。基于中医整体观念指导下的中药方剂对肺纤维化具有良好的治疗效果,因此基于VEGFR和FGFR探讨中药对COVID-19后遗症肺纤维化的干预作用具有重要意义。该研究运用分子对接技术,通过构建VEGFR和FGFR靶点的对接模型,以原配体-CDCOKER ENERGY打分值的80%为阈值筛选方剂中的活性成分,并寻找其来源中药。通过检索成分命中率高于30%中药的性味归经及功效信息,构建中药-归经网络及中药-功效网络,结合《新型冠状病毒肺炎诊疗方案(试行第七版)》中2首、《中医疫病名方精选》中9首针对疫病恢复期的方剂,探讨了中药方剂治疗肺纤维化的规律。研究结果显示,基于VEGFR和FGFR靶点筛选获得潜在抗肺纤维化的活性成分分别为959,1 047个。VEGFR和FGFR靶点成分命中率达到30%以上的中药为黄芩、南沙参、半夏、薏苡仁、陈皮、白扁豆、白芍、桑叶、党参、玉竹、芦根、柴胡、黄芪、人参、西洋参、玄参、当归、丹参。分析上述中药性味归经及功效信息可知,治疗肺纤维化的中药主归肺(degree=14)、脾(degree=8)经,功效以补虚(degree=9)为主。结合恢复期推荐处方进行分析,上述中药在恢复期方剂中均有出现,其中以气阴两虚处方与补中益气汤命中中药数目最多。本次新型冠状病毒肺炎的主要证候为湿热蕴肺,内蕴邪热久羁,易于耗气伤津,临床观察显示,恢复期患者多处于余邪未尽、正气尚未恢复的阶段,主要表现为肺脾气虚,结合该研究分析,新型冠状病毒肺炎患者在此阶段,应当注重扶正祛邪,健脾益肺,进而缓解病毒导致的肺纤维化症状。研究结果旨在为中医药治疗COVID-19恢复期后遗症肺纤维化提供数据参考,并为临床用药提供指导。     

Progress of Research on Organic Fibrosis with Traditional Chinese Medicine

Fibrosis is the remodeling and repair processes of chronic injuries. There are few effective therapies. Chinese medicine formula, the main pattern of traditional Chinese medicine(TCM) in clinic, applies a multi-component, multi-target and complicated approach in the treatment of diseases, and certainly shows good comprehensive therapeutic effects on fibrosis. In this review, the clinical study, effects and mechanism of action of Fuzheng Huayu recipe in the treatment of liver, pulmonary, and renal fibrosis was analyzed and evaluated. Meanwhile, based on the understanding of TCM pathogenesis for liver cirrhosis, this review will also briefly introduce the research of different classical Chinese medicine formulae with various functions in the treatment of experimental liver fibrosis induced by different methods, including comparing the efficacy, analyzing the action characteristics and mechanism of effective formulae, exploring pathological and biological basis of TCM diagnostic and therapeutic pattern, which will contribute to the research of TCM in the treatment of organ fibrosis.     

安宫牛黄丸及其演化方剂的临床研究进展

安宫牛黄丸是我国传统药物中治疗急重病症的久负盛名的良方,在中医临床上被誉为"温病三宝"之一。清开灵、醒脑静注射液等药物属于安宫牛黄丸的演化方剂。近5年来,安宫牛黄丸及其演化制剂在治疗急性脑卒中、颅脑损伤、昏迷、缺氧缺血性脑病、肺性脑病以及病毒性脑炎等疾病的临床应用中取得了不少新的研究进展,结果表明安宫牛黄丸及其演化制剂对于这些疾病具有较好的治疗效果,值得临床推广使用。     

放射性肺纤维化防治进展

随着近几年我国食管癌、乳腺癌,尤其肺癌等胸部恶性肿瘤发病率的不断上升,胸部放疗造成的放射性肺纤维化并发症因其发生上的必然性、发展过程的隐蔽性和结局的严重性而日益受到重视。为减轻放射性肺纤维化给患者带来的痛苦,国内外科研、临床人员围绕其发生机制、预防、治疗做了大量研究,但是结果均不令人满意。中医药防治放射性肺纤维化的研究为这一领域开拓了广阔的前景。     

Advances in traditional Chinese medicine for liver disease therapy in 2020

Liver diseases are gradually becoming a serious threat to human health worldwide.Although a number of medications have been introduced for the prophylaxis,diagnosis,and treatment of liver diseases,several limitations and challenges remain.Traditional Chinese medicine is frequently used to treat liver diseases and well known to protect hepatocytes and inhibit inflammation,oxidative stress,and fibrosis.However,given the complex composition of traditional Chinese medicine,clarifying the mechanisms behind its curative and protective effects is difficult.In this review,research progress on traditional Chinese medicine for the treatment of liver diseases in 2020 is summarized on the basis of the literature available in the PubMed database.Herbal extracts derived from traditional Chinese medicine,including flavonoids,polysaccharides,saponins,and alkaloids,and Chinese medicinal formulas,such as the classic decoctions Chaihu Shugan powder,Linggui Zhugan decoction,and Huanglian Jiedu decoction,have shown promising therapeutic efficacy in liver disease treatment.We summarized the findings of several studies on the active ingredients of traditional Chinese herbs used for liver disease treatment in 2020,focusing mainly on their ability to confer antiviral effects to treat hepatitis,regulate antioxidant levels and apoptosis to treat liver injury,inhibit inflammation and improve dysfunctions in amino acids and energy metabolism to treat alcoholic liver disease,reduce hepatic lipid deposition to treat nonalcoholic fatty liver disease,promote activated hepatic stellate cells to treat liver fibrosis,inhibit the proliferation or promote the apoptosis of liver cancer cells to treat hepatocellular carcinoma,and improve bile acid metabolism to treat cholestasis.     

Prevention of pulmonary fibrosis with salvianolic acid A by inducing fibroblast cell cycle arrest and promoting apoptosis

Ethnopharmacological relevanceDanshen (Salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine (TCM), often in combination with other herbs, to treat a diversity of ailments. More recent studies have focused on its possible roles in the treatment of respiratory diseases (pneumonia and pulmonary fibrosis) and found that it has pharmacological activity that protects pulmonary morphology and function. However, the mechanism underlying this activity has not yet been clarified.Materials and methodsThe purpose of this study was to investigate the anti-pulmonary fibrosis effects exerted by salvianolic acid A (SAA), the ingredient responsible for the pharmacological activity of Danshen, and the underlying mechanisms. Bleomycin (BLM)-induced rat pulmonary fibrosis was used to evaluate the antifibrotic role of SAA, and fibroblast cells were used to study the mechanism involved.ResultsBLM-treated rats exhibited increased alveolar wall thickness and collagen deposition in lung tissues, but these pathologies were greatly attenuated by daily administration of SAA. We also found that SAA significantly inhibited the proliferation, adhesion and migration of fibroblasts in vitro. This was partly due to a strong induction of cell cycle arrest and apoptosis upon SAA treatment. Consistent with these phenotypes, we observed decreased expression of the cell cycle-related proteins cyclin D1, cyclin E1, and cyclin B1, and increased expression of p53 and p21 in SAA-treated cells. In addition, the anti-apoptotic Bcl-2 protein decreased in a dose-dependent manner, while cleaved caspase-3 protein increased upon SAA treatment.ConclusionsThese results suggest that the alleviation of rat pulmonary fibrosis by SAA is due to the inhibition of fibroblast proliferation and induction of apoptosis, which occurs mainly through p53-dependent growth arrest and apoptosis. We suggest that SAA should be considered as a potential novel therapeutic agent for the treatment of fibrotic lung diseases.     

五法经典方辨治肝纤维化的现代药理作用研究概况

肝纤维化是以肝星状细胞（hepatic stellate cells,HSCs）激活和细胞外基质（extracellular matrix,ECM）异常沉积为特点的多种恶性肝脏疾病必经病理过程及影响疾病转归的重要因素。研究表明,众多临床常用经典方可通过调控HSCs命运、调节胆汁酸或脂质代谢、减少病理性血管生成、直接或间接促进ECM降解以发挥防治肝纤维化的重要作用。回顾并总结了近年来临床肝纤维化诊疗中的常见中医证型,在中医药辨证思维指导下归纳出利湿退黄、调和肝脾、养血柔肝、破瘀消癥、滋阴清热5种主要治法,并在此基础上总结对应经典方现代药理作用的研究进展,以期建立中医辨证理论指导下经典方治疗肝纤维化的独特治疗体系,并为临床提供肝纤维化创新性诊疗策略。     

特发性肺纤维化合并肺癌的中西医研究进展

现代医学研究表明,特发性肺纤维化合并肺癌发病机制可能是基因异常、细胞间通讯的减少、瘢痕、吸烟、炎症和职业粉尘接触污染,目前采用药物、手术、酪氨酸激酶抑制剂、基因治疗和去除衰老细胞等治疗方法。中医研究方面,该病为正气亏损,实邪阻肺所致,治疗以扶正固本,祛邪抗癌。本文从国内外近年来中、西医学关于特发性肺纤维化合并肺癌的研究现状出发,从中西医两方面,分别对该病的发病机制、临床特点和治疗方法进行综述,并对中医药治疗该病的发展趋势进行展望,为中西医结合治疗提供新的研究方向,以供读者学习和参考。     

中医治疗肺间质纤维化研究进展

肺间质纤维化是以进行性呼吸困难、喘息、气短、干咳、喘憋为临床表现,以限制性通气功能障碍、低氧血症、慢性进行性弥漫性肺间质纤维化为特点的肺间质性疾病。由于病因多样,发病机制复杂,临床有效治疗方法欠缺,肺间质纤维化已经成为呼吸系统疾病领域中最富挑战性的疾病。近年来中医药对该病的研究也渐成热点,通过对肺间质纤维化中医病名、病机以及治疗的阐述,为进一步探讨该病发病机理及提高临床疗效开拓思路。     

多元思辨模式在咳嗽诊疗实践中的应用与体会

咳嗽是一种常见病、多发病,中西医治疗一般都不难,但是咳嗽变异性哮喘、慢性阻塞性肺疾病及喉源性咳嗽等慢性肺系疾病病程较长,西医治疗比较棘手且取效不易。文章旨在通过3则咳嗽验案,介绍"审症(抓主症)-辨人(体质)-诊病-识证(方证)"四位一体的多元思辨模式在咳嗽诊疗实践中的应用,首当抓主症,次辨体质,明确诊断,从方证入手,谨守病机,遣方用药常以经方和后世经典方化裁治疗咳嗽,衷中参西,圆机活法,该思路和方法对于指导中医临证施治具有重要的参考价值。     

人参及其复方制剂防治肺病的研究进展

人参Panax ginseng是一种具有多种生理功能的传统药食两用植物,是临床上应用最多的中草药之一,有"百草之王"之称,其复方制剂如人参补肺汤、参麦注射液等被广泛应用于临床。研究表明人参及其复方制剂具有抗动脉粥样硬化、抗心肌缺血、抗肿瘤、抗肝纤维化等作用。在新冠肺炎爆发后,人参及其复方制剂被大量应用于肺损伤保护的临床及实验研究中,发现其对各种肺部疾病具有较好疗效。人参的主要活性成分是其诸多功效的物质基础,从人参皂苷等多种功效成分对人参及其复方制剂治疗肺病的作用及机制方面进行综述,为人参及其复方制剂在临床上发挥更加广泛的治疗作用及其抗肺病作用的深入研究提供参考。     

从“肝失疏泄”浅析肝与肺间质纤维化早期的相关性

近年来,肺间质纤维化的发病率呈上升趋势,该病是以进行性加重为主的呼吸困难、喘息、气短、刺激性干咳为主要临床表现,以限制性通气障碍、低氧血症、慢性进行性弥漫性肺间质纤维化为特点的间质性肺病,病变主要累及肺间质,也可累及肺泡上皮细胞及肺血管.目前西医治疗首选激素,效果并不理想.中医药在研究肺间质纤维化方面显示出了良好的前景.中医上讲“肝主疏泄气机”又讲“百病生于气”,故而可以说“百病生于肝失疏泄”.对肺间质纤维化早期的病机从“肝失疏泄”方面进行探讨,从肝的角度浅析两者之间的相关性具有一定实践意义.     

二陈汤研究进展

二陈汤出自成书于北宋的《太平惠民和剂局方》,是历代公认的祛痰剂祖方,该方组方严谨,配伍精当,即可理气,又能化痰,对痰饮证及相关疾病的疗效确切。近些年来,围绕此方的作用机制研究不断扩展与深化。根据收集的资料显示,近年来关于二陈汤的研究多与治疗呼吸系统疾病相关,即便是其他系统的疾病也往往通过中医理论"从肺论治",为疾病的治疗提供了新的思路。二陈汤的研究多数为二陈汤的加味或者合方,基于此,通过对研究资料的收集,发现呈现此特点的原因与历代医家的用药规律有关。药理学的研究成为当下的热门,常涉及多个信号传导通路,来探讨二陈汤的多靶点治疗作用。药理学研究也以对呼吸系统疾病的治疗作用为主,特别是慢性阻塞性肺疾病(COPD),研究内容尤为详尽。将从二陈汤的文献研究,临床研究,药理学研究等方面为二陈汤的研究进展做简要的概述。最新的文献研究对理解二陈汤的内涵大有裨益,而多位研究者通过最新的检测技术阐明了二陈汤在机体内的作用机制。     

肺痿中医证治相关问题探讨

肺痿是指肺叶痿弱不用的慢性虚损性肺系疾病,为多种肺系疾病的慢性转归,预后不佳。近年来,中医药治疗肺痿的研究作为一项热点,取得了一定的成果。本文从肺痿的病因病机、辨证分型、中医药治疗等方面进行概述,为肺痿的中医药治疗提供理论基础和依据。     

中医肺病学科内涵与外延

中医肺病学科不同于西医呼吸病学科,研究对象是肺系统疾病,内涵包括肺系统生长发育规律及影响因素(解剖定位、生理病理特点)、肺系统疾病病因病机、辨证论治、常见症状辨证要点、治则治法、预防及预后;疾病范围:与肺功能(主气、司呼吸、通调水道、朝百脉、主治节)有关类病证。外延可分为三类:1相近学科:中医基础理论学、中医诊断学、中医方剂学、中药学、中医内科学、临床药理学、中西医结合内科学等;2相邻学科:组织胚胎学、人体解剖学、生理学、病理学、生化学、医学免疫学、分子生物学、中医养生康复学、医学统计学等;3边缘学科:微生物学、生物化学、生物物理学、生物医学工程学、心理学、数学、化学等;西医肺脏病生理、病理、诊断及治疗方法、研究手段及进展亦为其外延部分。目前中医肺病学研究主要集中在肺气虚证的基础及临床、中医药防治肺胀(慢性阻塞性肺疾病)、中医药防治哮病(支气管哮喘)等。未来建设的核心是坚持以中医理论为指导,尤其是藏象理论,发挥中医特色和优势,在继承传统的基础上,积极吸收现代医学先进技术和方法,促进自身不断发展。     

中药多糖抗纤维化作用机制研究进展

纤维化的主要病变过程包括细胞外基质的过度沉积及肌成纤维细胞异常增多,由此引发多种器官的损伤,与肝硬化、糖尿病、高血压及心肌梗塞等疾病密切相关,严重时可导致癌变和死亡。尽管一些药物如糖皮质激素和抗氧化剂,已被用于治疗纤维化,但目前这些药物存在严重的不良反应,且其有效性和长期安全性仍存在争议,因此迫切需要寻找新的治疗途径。近年来的研究发现,中药多糖可通过多种途径发挥抗纤维化活性,其中包括调节脂质代谢、抗氧化、抗炎及调控肠道菌群等机制。通过对近年来中药多糖在抗纤维化作用机制方面的研究进展进行综述,为中药多糖在纤维化疾病预防及治疗领域的应用提供科学依据和实际参考价值。     

Protective roles of Cordyceps on lung fibrosis in cellular and rat models

Ethnopharmacological relevance

Cordyceps sinensis is a fungus used in traditional Chinese medicine as a tonic to soothe the lung for the treatment of fatigue and respiratory diseases.Idiopathic pulmonary fibrosis is a chronic, irreversible and debilitating lung disease showing fibroblast/myofibroblast expansion and excessive deposition of extracellular matrix in the interstitium leading to breathing difficulty. Our previous observation revealed a partial relief of lung fibrosis in patients suffering from severe acute respiratory syndrome (SARS). We hypothesize that Cordyceps has beneficial effects on lung fibrosis and the objective of this study is to explore the target(s) of Cordyceps in the relief of lung fibrosis in animal and cell models and to gain insight into its underlying mechanisms.

Material and methods

A rat model of bleomycin (BLM)-induced lung fibrosis and a fibrotic cell model with transforming growth factor beta-1 induction were employed in the studies.

Results

Reduction of infiltration of inflammatory cells, deposition of fibroblastic loci and collagen, formation of reactive oxygen species, and production of cytokines, as well as recovery from imbalance of MMP-9/TIMP-1, were observed in fibrotic rats after treatment with Cordyceps in preventive (from the day of BLM administration) and therapeutic (from 14 days after BLM) regimens. In a fibrotic cell model with transforming growth factor beta-1 induction, the human lung epithelial A549 acquired a mesenchymal phenotype and an increase of vimentin expression with a concomitant decrease of E-cadherin. This epithelial–mesenchymal transition could be partially reverted by cordycepin, a major component of Cordyceps.

Conclusion

The findings provide an insight into the preventive and therapeutic potentials of Cordyceps for the treatment of lung fibrosis.     

中药有效成分抗肺纤维化的研究进展

肺纤维化是一种具有破坏性的肺组织紊乱,以细胞外基质的过度沉积为特征。肺纤维化对人类健康的危害极大,但目前尚无理想的治疗方法,寻找新的治疗药物十分必要。近年来文献报道了许多天然产物具有抗肺纤维化的作用,本文对中药有效成分治疗肺纤维化的研究进展进行综述。