天津中医药大学学报  2021, Vol. 40 Issue (4): 524-532

文章信息

王媛媛, 张闻, 李逸轩, 朱彦, 杨剑
WANG Yuanyuan, ZHANG Wen, LI Yixuan, ZHU Yan, YANG Jian
益气活血方药在肺炎治疗中的应用及其用药规律解析
Application and regularity analysis of prescription for invigorating qi and promoting blood circulation in pneumonia treatment
天津中医药大学学报, 2021, 40(4): 524-532
Journal of Tianjin University of Traditional Chinese Medicine, 2021, 40(4): 524-532
http://dx.doi.org/10.11656/j.issn.1673-9043.2021.04.23

文章历史

收稿日期: 2021-03-30
益气活血方药在肺炎治疗中的应用及其用药规律解析
王媛媛1,2 , 张闻1,3 , 李逸轩1,2 , 朱彦1,2 , 杨剑1,2     
1. 天津中医药大学国家组分中药重点实验室, 天津 301617;
2. 天津中医药大学天津市中药药理学重点实验室, 天津 301617;
3. 江苏柯菲平医药股份有限公司, 南京 210000
摘要: 肺炎为临床呼吸系统常见疾病,其症状的轻微或严重程度与引起感染的病原体种类、患者的年龄和整体健康等因素有关。若肺炎早期未能加以控制,可能引发呼吸衰竭甚至严重并发症而危及生命。根据现有研究,中医益气活血法治疗肺炎能够通过抑制炎症级联反应、提高血氧饱和度、改善微循环及提高机体免疫等作用,达到减轻患者肺部炎症,提高肺功能的疗效,进而减少肺炎由轻症向重症的转化,降低病死率,有效改善患者的生活质量。研究通过归纳益气活血法治疗肺炎的临床用药,总结了益气活血方药在肺炎治疗中发挥的作用机制及用药规律,以期为益气活血法在肺炎,尤其是当下新型冠状病毒所致的病毒性肺炎提供中医药治疗的科学依据。
关键词: 益气活血    肺炎    临床应用    用药规律    新型冠状病毒肺炎    
Application and regularity analysis of prescription for invigorating qi and promoting blood circulation in pneumonia treatment
WANG Yuanyuan1,2 , ZHANG Wen1,3 , LI Yixuan1,2 , ZHU Yan1,2 , YANG Jian1,2     
1. State Key Laboratory of Component Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China;
2. Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China;
3. Jiangsu Carephar Pharmaceutical Co., Ltd., Nanjing 210000, China
Abstract: Pneumonia is a common respiratory disease in clinic, its symptoms are closely related to type of pathogen causes, age and health factors of patients. Failure control in early stage of pneumonia may lead to respiratory failure or even serious complications, finally endanger life. According to present investigations, pneumonia therapy with Chinese medicines for invigorating qi and promoting blood circulation can reduce lung inflammation and mortality, improve lung function and quality of life, further decrease conversion of pneumonia from mild to severe, by their inhibit inflammatory cascade reaction, improve blood oxygen saturation, promote microcirculation and body immunity effects. This study summarizes clinical applications, regularities, and mechanism of Chinese Medicines for invigorating qi and promoting blood circulation in pneumonia treatment, which may shed new lights for pneumonia therapy, especially for COVID-19 therapy.
Key words: Yiqi Huoxue    pneumonia    clinical application    medication laws    COVID-19    

肺炎(Pneumonia)是指终末气道、肺泡和肺间质的炎症,是世界范围内最常见的可导致死亡的传染性疾病之一,常出现的症状包括咳嗽、头疼、发烧等。中医认为,肺为娇脏,易为外邪所伤,感受风寒之邪易于入里化热,炼液为痰,痰热壅阻于肺,致肺气郁闭,日久气壅血瘀,感受风热之邪易耗气伤阴;痰热阻肺,气郁不达则血行受阻,致气滞血瘀;热邪灼伤肺金,伤及血络可致络伤血瘀;热邪阻遏,肺气不宣,正气衰微,血脉不行,又可致气虚血瘀[1]。肺炎在中医范畴属于肺热性疾病,主要是风热中毒,出现肺瘀证[2],痰、热、毒、瘀为其病机特点[3]

中医辨证治疗肺炎的常见治法包括养阴清肺法、补肺健脾法、宣肺化痰法、益气活血法等[4-8],其中,益气活血法可治疗肺炎导致的气虚血瘀,痰热闭肺,益气活血方药既可补益体内正气,扶正祛邪,同时改善肺内瘀阻,广泛应用于各种类型肺炎的治疗。目前已有文献报道了清热解毒类中药、健脾益肺中药等治疗肺炎的相关临床总结[9-11],而益气活血法治疗肺炎的临床案例分析及总结近年来却鲜有分析,因此本文从益气活血类方药在各类肺炎中的临床治疗案例入手,着重总结了益气活血方药的用药规律及高频单味药,以期获得益气活血法治疗肺炎的用药指导和临床支撑。

1 益气活血方药治疗肺炎的临床现状

根据发病原因分类,肺炎可分为感染性肺炎、理化性肺炎、变态反应性肺炎及间质性肺炎。西医对肺炎的治疗方法主要为针对病原的抗感染治疗及针对重症的激素治疗[12],而中医可根据肺炎的病因病机、不同证候从临床分期和辨证分型等多方面论治。

1.1 感染性肺炎

根据不同病原微生物,感染性肺炎主要可分为病毒感染性肺炎,细菌感染性肺炎,支原体或真菌感染性肺炎。

1.1.1 病毒感染性肺炎

2019年12月爆发的新型冠状病毒肺炎(COVID-19)就是一种由冠状病毒引发的感染性肺炎[13],多版新型冠状病毒肺炎临床诊疗方案中都推荐了中药益气活血相关的注射剂,如血必净注射剂用于重症或危重症患者的全身反应综合征或/和多脏器功能衰竭;生脉注射液和参麦注射液用于危重症患者的免疫抑制[14],其主要改善了患者发热、干咳、乏力及憋喘等症状[15-18]。而针对冠状病毒引发的严重急性呼吸综合征(SARS),魏葆琳、张军平等[19-20]运用自拟益气活血方(太子参、黄芪、丹参、赤芍等)或益气活血注射液(黄芪注射液+丹参注射液;化瘀通脉注射液+生脉注射液)联合西医常规治疗,发现中西医联合治疗有效率明显高于西药治疗组。杭敏等[21]观察蛭丹化瘀口服液的临床治疗有效率及在高热、咳嗽、气喘、肺啰音及肺部X线阴影等症状消失时间方面均优于病毒唑治疗组,且患者痊愈时间明显缩短。

1.1.2 细菌感染性肺炎

中医药治疗在肺炎球菌、金黄色葡萄球菌、铜绿假单胞菌等细菌引发的细菌性肺炎[22]中也发挥着重要作用。焦扬等[23]加用活血解毒方剂(丹参、黄芩、连翘等)及复方丹参注射液联合羟氨苄青素治疗耐药性细菌感染性肺炎效果良好。蔡玲[24]采用自拟益气通腑汤(党参、黄芪、茯苓、川芎、红花等)联合常规抗生素治疗急性呼吸窘迫症伴随细菌性肺炎,发现其在改善动脉血气指标、气道压力指标、呼吸次数和脉搏等临床症状方面均优于常规抗生素治疗。

1.1.3 支原体感染性肺炎

由肺炎支原体引起的急性肺部炎症发生率高,临床起病急且易发展为大面积肺实变并累及多组织器官。各中医医家根据其病因,治法皆不尽相同,主要包括宣肺止咳化痰、清热解毒、活血化瘀、养阴清热、清肺泻肝等[25]。刘晓冉、刘洪敏等[26-27]在阿奇霉素静滴治疗基础上,加用自拟健脾益气活血汤(黄芪、白术、丹参、桃仁等)治疗小儿支原体肺炎可显著提高总有效率,并大幅降低阿奇霉素造成的不良反应。于东游、杭敏等[28-29]研究发现采用阿奇霉素联合中药(川芎注射液、蛭丹化瘀口服液)治疗小儿支原体肺炎可显著提高临床治疗有效率,迅速减轻咳嗽、喘憋等症状,缩短病程。

1.1.4 医院获得性肺炎

医院获得性肺炎由于感染源难以辨别,归为其他类感染性肺炎。患病高危人群为老年人,易引发全身炎症反应综合征,且致死率高[30]。痰浊、血瘀均贯穿于疾病,临床上以益气活血化痰法作为其主要的治疗原则[8]。周铃[31]证明益气活血经典方补阳还五汤可维持获得性重症肺炎患者正常自主呼吸功能,加快重症患者恢复。俞兴群等[32]在西医常规标准治疗基础上加用益气活血注射剂(参麦注射液)治疗糖尿病合并医院获得性肺炎患者,多项指标均有显著改善且优于西医常规疗法。

1.2 理化性肺炎

理化性肺炎是因胸部恶性肿瘤放射性治疗后导致的肺部炎性并发症,造成肿瘤的临床治疗难度增加并严重影响患者生存率。理化性肺炎的中医治法可归纳为益气养阴、清热解毒、活血化瘀等7个主要治法[33]。刘秀芬等[34]以自拟益气活血方(黄芪、党参、鸡血藤、丹参等)对接受放疗的非小细胞肺癌患者进行治疗观察,并与肾上腺皮质激素治疗的对照组进行对比,治疗组患者放射性肺炎及纤维化的发生率显著低于对照组,显著改善了治疗组患者的用力肺活量(FVC)、肺一氧化碳弥散量(CLCO)等指标。

1.3 间质性肺炎

间质性肺炎为一种肺脏损伤性病变,可同时累及肺间质、肺泡腔等内皮细胞,其临床进展速度快,病死率较高。中医认为此病后期痰浊内闭,阻遏气机,宜用通阳行痹、益气活血之法[35-37]。陈来福、殷健等[38-39]以西医联合自拟益气活血汤剂(太子参、黄芪、丹参等)治疗间质性肺炎患者,结果显示加用中药方剂后治疗总有效率及患者肺功能显著提高。张雯等[40]采用自拟益气活血方剂(黄芪、丹参、百部、桑皮等)对儿童间质性肺炎患者进行观察治疗,治疗后患者症状显著改善,胸部X线显示肺纹理条索状或阴影消失,总有效率高达86.7%。

针对以上几种肺炎类型,就具体案例中代表性益气活血方药简要总结,对处方组成成分、临床改善指标、中西医联合治疗与单独西医治疗的有效率进行了归纳,见表 1

表 1 益气活血代表性方药治疗各类肺炎改善临床指标及有效率对比
2 益气活血方药对于肺炎的作用机制总结

益气活血方药应用于肺炎的临床治疗过程中,中药治疗均能显著改善发热、头晕、乏力、胸闷等临床症状,提高治疗有效率,且可减少西药造成的毒副作用及不良反应,改善患者生存质量及炎症介质释放、免疫修复、机体自主呼吸功能等多个临床指标[41-47],具体的作用机制主要总结为以下几个方面。

2.1 有效抑制细胞肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1、IL-6等炎性因子释放,减轻全身过度炎症反应

潘东风等[48]研究发现复方丹参注射液可有效防治放射性肺炎,调控血浆IL-6及转化生长因子β(TGF-β)含量。陈国钟[49]采用头孢曲松钠及左氧氟沙星注射液静脉滴注基础上加用活血清肺汤,可明显抑制体内炎性因子IL-1、IL-6和TNF-α的释放。包春就等[50]研究发现在常规抗感染、祛痰、肾上腺皮质激素治疗基础上加用血必净注射液治疗小儿重症肺炎的有效率显著提升,患者机械通气时间和住院日明显缩短且患者炎症因子IL-6、IL-8、TNF-α水平明显降低。

2.2 不同程度改善血液流变性,促使全身微循环畅通,提高机体耐缺氧能力

黎辰等[51]加用丹参注射液中西医结合治疗细菌性肺炎,治疗组总有效率显著高于对照组,丹参注射液具有活血化瘀的功效,能改善炎症部位的充血、水肿,对于改善充气与血流之比具有积极意义。刘晓红等[52]通过蛭丹化瘀口服液辅助罗红霉素治疗支原体肺炎小鼠可减少小鼠肺组织内血栓数,改善微循环。

2.3 增强机体免疫力

王智等[53]应用益气活血化痰法(参麦注射液+丹参酮ⅡA磺酸钠注射液+痰热清注射液)治疗重症医院获得性肺炎,可有效提高患者动脉血氧分压,增加患者免疫球蛋白G(IgG)和免疫球蛋白M(IgM)表达水平,增强机体免疫力,不仅阻止了病情发展及恶化,还可提高患者存活率及生存质量。陈不尤[54]采用自拟活血药物组方(黄芪、当归等)治疗肿瘤的复发率和转移率明显低于抗生素加激素治疗组,中药兼顾全身扶正,增强机体免疫,更具优越性。长期随访发现,益气活血方配合放疗还可提高患者机体免疫力,减少骨髓抑制,提高肺癌患者的生存期[55]

3 益气活血方药治疗肺炎的用药规律

此综述针对肺炎治疗过程中所用益气活血方药进行总结及归纳,以此分析得出益气活血法治疗肺炎的用药规律。作者通过检索文献,并建立用药数据库,并统计了益气活血方药中常用中药的用药规律及其配伍。

3.1 单味中药使用频率分析

文中除一些自拟的益气活血方药外,常用一些中药益气活血中成药如生脉注射剂、化瘀通脉注射液、蛭丹化瘀口服液等,共涉及30方,63味药,用药总频次为276次,其中单味药用药频率出现3次以上者共29种,主要涉及益气、活血、清热、生津、润肺、化痰、利湿、祛风、理气9类。在中药组方的高频单味药分析中,黄芪、丹参、川芎、当归、桃仁、赤芍作为益气活血药物应用频率位于前6位。在应用益气活血法治疗肺炎过程中,益气类药物以黄芪为主,用药频率高达53.3%,另外,白术、党参也为益气类常用药;活血类中药以丹参最为常用,用药频率高达56.7%,川芎、桃仁、当归等活血药也常用于益气活血方药中肺炎的治疗。其他类中药,如清热类药、润肺类药、化痰类药等用药频率介于10%~30 %,为益气活血方药治疗肺炎的较常用辅助治疗药物。见表 2

表 2 益气活血方药中常见配伍药味治疗肺炎的用药频次分析
3.2 高频中药关联规则分析

作者进一步利用Clementine 12.0统计软件对益气活血方药中的药物进行关联规则分析,使用Apriori建模,进一步挖掘不同中药之间的配伍关系,设置支持度为30 %,置信度为50 %,最大前项数为3等条件挖掘出常用方剂中的潜在药物组合,共计得到核心药物组合9组。见表 3

表 3 益气活血方药常用药物配伍间的关联规则分析

按药物组合出现的频次将药对由高到低排序,前4位分别是黄芪-丹参、当归-川芎、赤芍-川芎、黄芪-川芎,其中黄芪-丹参为益气活血治疗肺炎中主要用药组合,与表 1中单味药出现频率分析结果一致。从图 1药物间网络化关联中进一步分析显示,益气药以黄芪为主,其中丹参、桃仁、川芎、赤芍、当归等均为其常用配伍的活血中药。

图 1 益气活血方药常用药物之间网络化关联展示(n≥6)
4 展望

肺炎的病位在肺,传变规律及辨证治疗多循温病的卫气营血理论。在肺炎的传变阶段,一些治法如清热解毒、活血化瘀、祛痰及专方专药的应用,都取得较好效果。大量的临床案例证明,中医药早期介入更能充分体现和发挥中医药善于“调养”的特长,扬长避短、优势互补,使中西医结合达到较完美效果。其中,益气类中药具有调节机体免疫功能,促进非特异性免疫反应,促进细胞和吞噬细胞的吞噬功能并兴奋网状内皮系统等作用;活血类中药除具有抑制病原微生物生长、解毒消炎作用外,还可降低血液粘稠度,使聚集的红细胞解聚,加快微循环流速,提高组织从微循环中摄取氧的能力,终止感染过程,有利于组织的修复[56]。如对新冠肺炎感染的肺炎重症或危重症新冠肺炎患者,中医药整体治疗显示出显著的免疫抑制作用,且在恢复期可促进组织修复。

本文归纳了常用益气活血法治疗各类型肺炎的临床案例,重点探讨总结了其中出现的30首益气活血中药复方,发现用药频率排在前6位的药物依次为丹参、黄芪、川芎、当归、赤芍、桃仁。其中,补气药黄芪、白术、党参这3味药,性味以甘温或甘平为主,多归脾、肺经,补益脾肺之气,多用于肺炎的治疗。搭配活血药物,其中黄芪-丹参、黄芪-川芎、川芎-当归等配伍药对高频使用,能达到增强体内正气,减轻肺内瘀阻的目的。通过进一步文献搜索,发现丹参中丹参酮可通过其抗氧自由基作用,提高治疗小儿支原体肺炎的临床疗效[57];黄芪中的黄芪甲苷可以通过增强HINI病毒性肺炎中的巨噬细胞自噬来减少白细胞介素1β(IL-1β)的分泌[58];川芎中川芎嗪通过调节机体免疫环境治疗耐药性大叶肺炎[59];赤芍中的芍药苷对肺炎克雷伯菌有显著的抑制作用[60]

益气、活血药物的作用机制互相补充,共同构成益气活血法治疗肺炎的药理学基础;同时在其他清热、润肺、化痰等药物的共同配伍应用中充分体现了中药多靶点、多途径的治疗特点,对于肺炎的辨证论治起到了不可或缺的作用。益气活血方药在肺炎治疗不同阶段中均可有效改善其临床症状,加快痊愈进程,本研究通过对益气活血方药治疗肺炎的用药规律总结,得到应用益气活血法治疗肺炎的常用中药,以期为其临床治疗提供理论支持及用药指导。

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