Network Biological Modeling:A Novel Approach to Interpret the Traditional Chinese Medicine Theory of Exterior-Interior Correlation Between the Lung and Large Intestine

Objective To study the common pathogenesis of pneumonia and colitis using modern biological network analysis tools,and to explore the theory that the lung and large intestine are exteriorly and interiorly related.Methods The relevant target genes(hereinafter,“targets”)of pneumonia and colitis were separately queried on the GeneCards database.The main targets of the two diseases were then screened out according to their correlation scores and intersected to obtain those common to the two diseases.Metascape was used to analyze the main and common targets identified,and the Database for Annotation,Visualization and Integrated Discovery(DAVID)was used to enrich and analyze the common targets.Cytoscape 3.7.2 software was used to build the network diagram.Results In total,54 targets,such as TNF,IL-10,IL-6,IL-2,IL-4,TLR4,TLR2,CXCL8,IL-17A and IFNG,etc.,are common to pneumonia and colitis,which are mainly enriched in these processes such as cytokine–cytokine receptor interaction,the Tcell receptor signaling pathway,the Toll-like receptor signaling pathway and the Jak-STAT signaling pathway.The Metascape modular analysis identified 11 modules for pneumonia,six modules for colitis,and two modules for the common targets.Conclusions Pneumonia and colitis have the same pathogenic targets and mechanisms of action and finally interact with each other through inflammatory reactions and immune responses.This provides a probable molecular mechanism that explains the theory that the lung and large intestine are exteriorly and interiorly related.

Infrared Thermal Imaging-Based Research on the Intermediate Structures of the Lung and Large Intestine Exterior-Interior Relationship in Asthma Patients

Objective: By observing body surface temperature variation of the intermediate structures of the Lung(Fei) and Large Intestine(Dachang) exterior-interior relationship in asthmatic patients, to investigate the pathological response on the pathway of channels and to substantiate the objective existence of the intermediary structures. Methods: The study included 60 subjects meeting the bronchial asthma inclusion criteria(experimental group) and 60 healthy subjects(normal control group). ATIR-M301 infrared thermal imaging device was used for detecting body surface temperature of the subjects and collecting the infrared thermal images. The temperature values of the intermediate structures of Lung and Large Intestine exterior-interior relationship [throat, Quepen, elbow, nose, Lieque(LU 7), Pianli(LI 6)], control areas(0.2 cm lateral to the above structures) and Yintang(EX-HN 3) were measured on the infrared thermal image by infrared imaging system. Then, the above temperature values were compared and analyzed within and between two groups. Results: There were insignificant differences between the temperature on the left and right sides of the intermediate structures(Quepen, elbow, LU 7, LI 6) in normal control group(P>0.05). Except for that of Quepen, there were insignificant differences between the temperature of the intermediate structures and their corresponding control areas in normal control group(P>0.05). In the experimental group, the temperature on the left and right sides of the intermediate structures(Quepen, elbow, LU 7, LI 6) showed statistically significant differences(P<0.05 or P<0.01); the temperature difference between intermediate structure(throat, Quepen, elbow, nose, LI 6) and their respective control areas were also significant(P<0.05 or P<0.01). The temperature of the intermediate structures(throat, Quepen, elbow, LU7, LI 6) between the experimental group and normal control group showed significant differences(P<0.05 or P<0.01). Conclusions: This study is an initial step to validate the objective existence of Lung and Large Intestine exterior-interior relationship intermediate structures, as described in the Chinese classical medical literatures, through the functional imaging angle. The intermediate structures are the pathological reaction areas of the bronchial asthmatic patients.

The influence of intestine-based treatment using Xuan Bai Cheng Qi Tang on the concentration of trace elements in the main organs of COPD rats

Objective:To test two theories from traditional Chinese medicine:'exterior -interior relationship between the lung and large intestine' and 'treating from the intestine principle for lung disorders'.The influence of intestine-based treatment using Xuan Bai Cheng Qi Tang (XBCQT) on the concentration of three trace elements-copper (Cu),zinc (Zn),and manganese (Mn)-was observed in the tissues of the lung,small intestine,large intestine,and stomach of rats suffering from chronic obstructive pulmonary disease (COPD).Methods:Thirty-five male Wistar rats were divided randomly and equally into five groups:control;model;Fei treatment (A);Chang treatment (B);and Fei-Chang treatment (C).A rat model of COPD was prepared by tracheal injection of lipopolysaccharide plus exposure to cigarette smoke.Treatments with medicinal herbs started day-22 of administration and exposure to cigarette smoke for 7 days.The control group and model group were administered physiologic (0.9%) saline solution via the stomach.After 7 days of intervention,the tissues of the lung,small intestine,large intestine,and stomach were removed.Inductively coupled plasma-atomic emission spectroscopy was used to detect the levels of Cu,Zn,and Mn in those tissues.Results:Compared with the control group,the Cu concentration in the tissues of the small intestine,large intestine,and stomach increased significantly in the model group (P <.05);the Mn concentration in the tissues of the lung,large intestine,and stomach increased significantly in the model group (P <.05);the Zn concentration in the tissues of the lung and large intestine decreased significantly in the model group (P <.05).In comparison of the model group:the Cu concentration in the tissues of the lung and large intestine decreased significantly in the B group (P <.05);the Mn concentration in the tissues of the lung,small intestine,and large intestine decreased significantly in the B group (P <.05);the Zn concentration in the tissues of the lung,small intestine,and large intestine increased significantly in the B group (P <.05).For the A group versus C group comparison,the Zn concentration in the tissues of the small intestine and stomach increased significantly in the latter (P <.05).Conclusion:This study showed that 'treating from the intestine' using Xuan Bai Cheng Qi Tang and its modified formulae can regulate the concentration of trace elements in the main organs of COPD rats.This may be one of the mechanisms for intestine-based treatment for COPD.

杨燕教授从肺论治儿童功能性便秘的临床经验

儿童功能性便秘约占小儿便秘的95%以上,是小儿消化系统的常见病,病程迁延易对儿童的身心健康产生严重影响。文章总结杨燕教授治疗儿童功能性便秘的临床经验。杨燕教授认为便秘的病机主要是大肠的传导功能失常,但与肺脏密切相关。肺与大肠相表里,肺气亏虚或肺气郁闭,宣肃失职,气机不畅,津液疏布失常,肺热移于大肠,肠失濡润,均可导致便秘发生。从肺论治,临证采用塞因塞用之法补气启闭治虚秘,提壶揭盖之法理肺通腑治实秘,同时重视良好的饮食结构及日常护理,临床疗效显著。附验案1则以佐证。

基于“肺与大肠相表里”探析血管内皮细胞与肠道菌群的关联

肠道菌群及其代谢物失调对内皮细胞损伤和功能障碍具有重要影响。中医“肺”与血管内皮细胞在结构、生理及病理方面具有相关性。中医学“肺与大肠相表里”理论是肺与肠在结构、生理及病理方面相关性的高度概括,可作为血管内皮细胞与肠道菌群相关联的理论基础。本文可为以肠道菌群为切入点、修复血管内皮细胞损伤干预心血管疾病的实验研究提供理论依据,并为中医药临床治疗相关疾病提供参考。

The Association between Pulmonary Function Impairment and Colon Inflammation in Ulcerative Colitis Patients： A Scientific Basis for Exterior-Interior Correlation between Lung and Large Intestine

Objective： To investigate the involvement of pulmonary function impairment in ulcerative colitis（UC）, and explore a scientific basis for the Chinese medicine（CM） theory of exterior-interior correlation between Lung（Fei） and Large intestine（Dachang）. Methods： Totally 120 patients with a diagnosis of UC were recruited and the demographics, clinical data, and blood samples were collected. C-reactive protein（CRP） and erythrocyte sedimentation rate（ESR） concentrations were measured. Every patient accepted pulmonary function test and took chest radiograph（CXR）. Results： Pulmonary function abnormalities were present in 72 of 120 patients. The median（interquartile range） vital capacity（VC）, forced vital capacity（FVC）, forced expiratory volume in 1 s（FEV_1）, carbon monoxide diffusion capacity（DL_∞） of lung, total lung capacity（TLC） and functional residual volume（FRV） were decreased in distal UC and pancolitis compared with ulcerative prochitis（P〈0.0005）. Male patients had increased VC, FEV_1/FVC, and residual volume（RV）/TLC compared with female（P〈0.0005）, but decreased DLCO and carbon monoxide iffusion capacity（KCO） of lung/alveolar ventilation（P〈0.0005）. Age was strongly correlated with RV（Spearman rank correlation coefficient（rs）=–0.57, P〈0.0001）, and RV/TLC（rs=0.48, P〈0.0001）. Age was also correlated with FEV_1/FVC（rs=–0.29, P=0.001）, forced expiratory flow in 75% vital capacity（FEF75%, rs=–0.20, P=0.03）, DLCO（rs=–0.21, P=0.02）, TLC（rs=–0.25, P=0.006）, and FRV（rs=–0.28, P=0.002）. The course of disease was correlated with FEF75%（rs=–0.18, P=0.049） and KCO（rs=–0.19, P=0.036）. Chest radiograph abnormalities were presented in 38 of 120. Pulmonary symptoms were presented in 10 of 120. Other extraintestinal complications were presented in 21 of 120. Conclusions： Pulmonary function impairment was more frequently than other extraintestinal complications in UC patients, which may be affected by sex, age, extent and course of disease. These results may be a scientific basis for the theory of exterior-interior correlation between Lung and Large intestine.

从肠论治脓毒症所致ALI/ARDS有效性的Meta分析

目的系统评价在中医“肺与大肠相表里”理论下指导下,从肠论治脓毒症所致急性肺损伤/急性呼吸迫综合征(ALI/ARDS)的临床疗效,为临床提供循证参考。方法通过计算机检索中国知网(CNKI)、万方数据库、维普中文期刊数据库、中国生物医学文献数据库(CBMdisc)荷兰医学文摘Embase数据库、美国国立医学图书馆PubMed数据库、Cochrane图书馆数据库中,从建库至2020年10月8日发表的将通腑法作为干预措施治疗脓毒症所致ALI/ARDS的随机对照试验(RCT)。对照组采用常规西医治疗,试验组在常规西医治疗基础上联合通腑法治疗。由2名研究者筛选文献并对符合纳入标准的文献进行数据提取,运用改良Jadad量表进行质量评价,采用RevMan5.4和Stata16.0软件对数据进行Meta分析。结果最终纳入13篇文献,均为单中心RCT,其中≥4分的文献7篇,<4分的文献6篇。共纳入579例患者,其中试验组290例,对照组289例。Meta分析显示,与对照组比较,联合通腑法治疗能明显提高脓毒症所致ALI/ARDS患者氧合指数[PaO_(2)/FiO_(2),均数差(MD)=62.55,95%可信区间(95%CI)为55.74~69.37,P<0.05],降低白细胞介素-6(IL-6,MD=-29.70,95%CI为-48.34~-11.06,P<0.05)、肿瘤坏死因子-α(TNF-α,MD=-2.94,95%CI为-5.28~-0.59,P<0.05)降钙素原(PCT,MD=-1.34,95%CI为-2.17~-0.51,P<0.05)和C-反应蛋白(CRP,MD=-22.41,95%CI为-36.52~-8.29,P<0.05)水平,缩短机械通气时间(MD=-2.26,95%CI为-2.86~-1.66,P<0.05)和重症监护病房(ICU)住院时间(MD=-4.15,95%CI为-7.47~-0.84,P<0.05),降低28d病死率[相对危险度(RR)=0.43,95%CI为0.24~0.76,P<0.05]和急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ,MD=-3.53,95%CI为-5.41~-1.64,P<0.05)。结论从肠论治对减轻脓毒症所致ALI/ARDS患者病情及改善预后有一定价值,但仍需进一步开展高质量的RCT以验证其疗效,为临床治疗提供更准确的循证医学证据。

从“肺-肠”轴角度探讨肠道菌群与过敏性鼻炎的关系

过敏性鼻炎属于全球高发的气道变应性疾病,较多人群深受其影响,关于其更安全有效的治疗方式仍不断被探寻与挖掘。近年来关于肠道微生态与肺部疾病的相互关系被深入研究,文章基于肺肠关系,结合中医“肺与大肠相表里”理论,并从西医胚胎发育、菌群微环境、内分泌代谢、黏膜免疫等角度探讨肺-肠关系,在此基础上,认为肠道菌群可从细胞因子免疫平衡、机体黏膜等方面影响过敏性鼻炎的发生发展,以期为临床治疗过敏性鼻炎提供更多思路。

“肺与大肠相表里”物质相关性的研究进展

中医药文化历史源远流长,作为中医药藏象理论的重要组成部分,“肺与大肠相表里”阐述了肺-肠来源相同,生理上相互协作,病理上和治疗上相互影响。现基于“肺与大肠相表里”理论,分别从经络、津液代谢、黏膜免疫及肠道运动等方面探讨肺-肠物质相关性,为临床治疗肺肠相关疾病提供参考。

Experimental Study on the Mechanism of Protective Effect of Free Fu on Gut-derived Endotoxin-Mediated Lung Damage

The effect of tumor necrosis factor-α (TNF-α) on endotoxin (ET)-mediated lung damage caused by incomplete ligation of large intestine and the influence of free Fu on the expression of TNF-α mRNA were explored. Forty SD rats were randomly divided into 4 groups: normal control group, model group, ligation group and treatment group (n=10 in each group). The models were made by the method of partly ligating the rectum outside the body. The plasma level of lipopolysaccaride was measured by dynamic nephelo metric method and the serum level of TNF-α was detected by the method of radioactive immunity. The expression of TNF-α mRNA in lung tissue was detected by RT-PCR method. The results were compared among the 4 groups. The results showed the plasma levels of ET and serum TNF-α in the model group and the expression of TNF-α mRNA in the lung tissues were remarkably higher than those in the normal control group (P<0.01). After the treatment of free Fu, all of the above indexes in the treatment group were all decreased as compared with model group (all P<0.01), and the damage to lung was alleviated. It was concluded that TNF-α might play a very important role in the ET-mediated lung damage caused by incomplete ligation of large intestine, free Fu could protect the lung from damage.

肠道菌群与儿童呼吸系统疾病

近年来,随着呼吸系统疾病与肠道菌群相关性研究的增多,中医“肺与大肠相表里”理论和现代医学“肺-肠”轴概念逐渐受到国内外学者的重视。对感染性肺炎、哮喘、过敏性鼻炎等儿童呼吸系统常见病与肠道菌群的相互影响进行了归纳总结,并结合中医药诊治理念及方法为中医理论“肺与大肠相表里”的科学阐释提供参考。

近20年中医“肺肠同治”临床应用可视化分析

目的分析总结“肺肠同治”理论的研究现状、研究热点及发展趋势,从而为该领域后期的研究提供参考。方法检索中国知网(CNKI)、万方数据库(Wanfang)和维普(VIP)中文数据库,自2004年1月1日-2023年4月30日期间收录的相关文献,利用CiteSpace、VOSviewer及Microsoft Excel软件对文献的发文年度、作者、研究机构及关键词进行可视化分析,并绘制知识图谱。结果共获得944篇文献,其中学术期刊751篇,硕博论文193篇。该领域论文共涉及作者2118名,其中发文量超过10篇的作者有23位,涉及的研究机构大部分是中医院校。近年来研究热点集中在肺与大肠的临床应用上,包括该理论指导下的疾病类型、治法、方药等。结论肺肠同治理论研究正处在上升阶段,对肠道菌群、代谢组学的研究可能是未来的研究趋势。

调补肺肾三法对慢性阻塞性肺疾病稳定期大鼠肺与肠道炎症指标的影响

目的探讨调补肺肾三法对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)稳定期大鼠肺与肠道IL-6、IL-33和IFN-γ的调控。方法将60只SD大鼠随机分为空白(Control)组、COPD模型(Model)组、补肺健脾(Bufei Jianpi,BJ)组、补肺益肾(Bufei Yishen,BY)组、益气滋肾(Yiqi Zishen,ZS)组和氨茶碱(aminophylline,Am)组。第1-8周,采用香烟烟雾暴露联合脂多糖(lipopolysaccharide,LPS)滴注法制备稳定期COPD大鼠模型,对应给予生理盐水、补肺健脾方、补肺益肾方、益气滋肾方、氨茶碱灌胃4周,于第13周灌胃周期结束后取材。光镜下观察肺与结肠组织形态学改变,采用免疫组化法(IHC)对肺与结肠组织中白细胞介素(interleukin,IL)-6、IL-33、干扰素(interferon,IFN)-γ蛋白进行定位与半定量观察。结果与Control组相比,Model组大鼠不仅支气管周围与肺泡腔出现大量炎症细胞及炎性渗出,结肠黏膜也出现了大量炎症细胞浸润,肺和结肠IL-6、IL-33和IFN-γ水平明显升高(P<0.05,P<0.01);与Model组相比,各治疗组不仅支气管和肺泡炎症细胞浸润减少,而且结肠黏膜炎症细胞也出现减少,肺与结肠中IL-33和IFN-γ、结肠IL-6水平均明显降低(P<0.05,P<0.01),BY、ZS、Am组肺IL-6水平显著降低(P<0.01)。肺IL-6与结肠IL-6水平呈正相关,肺IL-33与结肠IL-33水平呈正相关,肺IFN-γ和结肠IFN-γ水平呈正相关。结论调补肺肾三法均可以改善慢性阻塞性肺疾病稳定期大鼠肠道功能障碍,其机制可能与抑制肺与结肠中IL-6、IL-33和IFN-γ的释放,降低肺与肠道炎症反应有关。

基于“肺与大肠相表里”理论探讨肠道微生态与糖尿病的关系

2型糖尿病(type 2 diabetes mellitus,T2DM)是一种以全身代谢紊乱为临床表现的代谢综合征,T2DM的发生常被认为与胰岛素分泌不足或机体产生胰岛素抵抗(insulin resistance,IR)有关,但其具体病因和发病机制目前尚不明确。糖尿病属中医“消渴”范畴,因病位不同分为上、中、下三消,其中上消病位在肺。许多归肺经的中药对消渴病具有确切疗效,而肠道菌群与糖尿病发生发展密切相关,加之“肺与大肠相表里”的经典理论,提示肺、肠道菌群与糖尿病之间存在某种内在联系,其中肺为水之上源,大肠主津,消渴病亦是以“三多一少”为主要临床表现,可见津液代谢为三者之间的重要纽带。文章系统梳理了肺与大肠的关系,总结了基于调控肠道菌群治疗糖尿病的现代药理学研究成果,归纳了肺与糖尿病的相互作用,从而对三者的内在关联进行佐证,试图阐明传统中医药从肺论治糖尿病的理论基础及“肺与大肠相表里”的现代科学内涵,为基于调控肠道菌群治疗糖尿病相关药物开发及其作用机制研究提供科学思路与理论依据。

调控免疫:从肺论治炎症性肠病的新思路

炎症性肠病(Inflammatory Bowel Disease,IBD)是一种慢性非特异性肠炎性疾病,包括溃疡性结肠炎(Ulcerative Colitis,UC)和克罗恩病,它以反复发作的腹痛、腹泻及黏液脓血便为主要症状。目前医学界认为其发病原因可能与遗传、环境和肠道黏膜对肠道内细菌的免疫失调等因素有关,免疫因素可能是占主导的发病因素。中医学认为肺与肠在生理、病理上密切相关,古代医家提出“肺与大肠相表里”的理论,认为很多大肠病证可以从肺论治,为从肺论治IBD提供了中医理论依据。IBD在中医学中属于“泄泻”“肠澼”“痢疾”等疾病范畴。病机多以脾胃虚弱为本,病位虽在大肠,但亦与其他脏腑,如脾、肺、肾等密切相关。根据“肺与大肠相表里”理论化生出从肺论治IBD的方法,临床治疗取得了显著疗效。同时,国内外现代医学研究也证实了肺与大肠在免疫学功能上存在诸多联系,并有研究表明从肺论治IBD可以获得显著的疗效,为未来深入挖掘肺与肠之间的免疫学联系和交流,以及对于IBD的治疗,都提供了新思路与新途径。

基于肺与大肠相表里理论论治溃疡性结肠炎

溃疡性结肠炎是一种慢性炎症性肠病,属于中医学泄泻、痢疾、肠澼等范畴。中医认为肺与大肠在经络、生理以及病理方面关系密切,提出从肺论治肠道疾病。本文从肺与大肠经络相关、气机宣降、津液代谢及现代肺肠轴理论等方面,论述从肺论治的可行性,为治疗溃疡性结肠炎提出新的诊疗思路。

基于“肺与大肠相表里理论”的中医方法治疗儿童支原体肺炎的临床效果评价

目的探究与分析基于“肺与大肠相表里理论”的中医方法治疗儿童支原体肺炎的临床效果评价。方法采取随机数表法将2020年1月—2022年5月聊城市中医医院收治的120例儿童支原体肺炎患儿分为对照组与观察组,各60例,对照组给予常规西药阿奇霉素治疗,观察组在对照组基础上加用鱼金注射液+复方丹参注射液+生大黄治疗,两组均连续治疗1个月。对比两组疗效、主要症状积分、肺功能及免疫功能指标,同时观察不良反应发生率。结果观察组的临床总有效率明显高于对照组(P<0.05);治疗后观察组与对照组相比,发热、咳嗽、痰壅及喘促评分均较低,最大呼气中段流量(MMEF)、50%肺活量最大呼气流量(MEF50)及25%肺活量最大呼气流量(MEF25)水平均更高,免疫球蛋白A(IgA)升高,免疫球蛋白G(IgG)、免疫球蛋白M(IgM)及免疫球蛋白E(IgE)均降低,差异有统计学意义(P<0.05)。两组患儿在治疗期间均未发现明显的不良反应。结论基于“肺与大肠相表里理论”治疗儿童支原体肺炎可明显促进患儿临床症状及体征的缓解,改善肺功能,提高机体免疫功能,且治疗期间无明显不良反应,安全性较高。

从“肺肠合病”模型大鼠血清TNF-α、IL-1含量变化探讨“肺与大肠相表里”

目的:建立肺病、肠病、肺肠合病大鼠病理模型,通过观察其血清TNF-αI、L-1含量情况,探索"肺与大肠相表里"相关病理机制。方法:实验设正常对照组、肺病组(过敏性哮喘)、肠病组(便秘)和肺肠合病组(过敏性哮喘合便秘)共4组。结果:与正常对照组比较,肺病组、肠病组、肺肠合病组大鼠血清TNF-αI、L-1含量均呈显著性差异(P<0.01);与肺病组比较,肺肠合病组大鼠血清TNF-αI、L-1含量呈显著性差异(P<0.01);与肠病组比较,肺肠合病组大鼠血清TNF-αI、L-1含量呈显著性差异(P<0.01)。结论:肺肠合病组大鼠血清TNF-αI、L-1含量均明显高于肺病组及肠病组,证实TNF-αI、L-1可能是肺与大肠相关的共同物质基础,为"肺与大肠相表里"理论提供一定的现代医学实验依据。

肺肠表里相关疾病证候特征分析

目的:探讨以"肺与大肠相表里"理论为指导,肺肠表里相关疾病的证候特征。方法:检索近30年公开发表的"肺与大肠相表里"肺系肠系疾病临床文献,利用描述性统计方法,分析其症状、证候及证候要素分布规律。结果:肺系疾病和肠系疾病,在症状上,往往是肺系与肠系症状并见。肺系疾病最常见的证型是痰热壅肺,肠系疾病最常见的证型是肺气亏虚,病位因素涉及最多的脏腑都是肺和肠。在病性因素中,肺系疾病最常见的病理因素是痰和热,肠系疾病最常见的因素是气虚。结论:肺肠表里相关疾病,证候特征在一定程度上有共同之处。肺与大肠的关系实质就是表和里、脏和腑的关系,肺病治肠、肠病治肺、肺肠同治,是其在治疗上相互为用的具体体现。

肺与大肠相表里的理论探讨和临床运用

文章对肺与大肠相表里的理论渊源、现代机理、临床应用三方面进行论证。"肺与大肠相表里"理论自《内经》以来,其科学性为历代医家的医疗实践所证明,具有较高的临床指导价值。现代研究证实,肺与大肠的相关性可以体现于胚胎发育、气体排泄途径、内分泌物质的影响、肠源性内毒素的作用、公共黏膜免疫系统等方面。临床研究方面,从肺病治肠、肠病治肺、肺肠并治进行治疗,均取得显著疗效,说明该理论对指导临床应用有很大意义。但是"肺与大肠相表里"的物质基础目前尚不明确,有待于系统研究、深入挖掘该理论在临床治疗中的应用价值。