Path-physiological Study On Impairment Of Clearing And Descending Function Of The Lung And Its Clinical Guiding Meaning

1. The Reasons and objective of the researchIn the new century, during the process of all-round modernization of traditionalChinese medicine, research on the basic theories of traditional Chinese medicine fallsbehind that of clinic and Chinese herbs obviously, and this severely affect its guidanceon clinic and the process of whole modernization of traditional Chinese medicine.Irregularity of terminologies, murkiness of concepts and incertitude ofmeanings are the outstanding problems in the basic theories of traditionalChinese medicine. How to research the meanings and essence of these conceptsby using modern scientific and technological ways and to accelerate thedevelopment of basic theories of traditional Chinese medicine is the primaryassumption of this research. Research on the ascending and descending functionsof the lung qi has always been a weak aspect of Zangxiang theories of traditionalChinese medicine. Our tutor lead us to carry out the path-physiological researchon the lung qi and its effect on guiding clinical work of traditional Chinesemedicine from this aspect combing his teaching, researching and clinicalexperience. We have been carrying out the following researches for many years,such as discussion on the lung dominates the skin and hair, research on thedescending and ascending functions of the lung qi. Meanwhile, think about theexperience of traditional Chinese medicine on dealing with SARS in the earlieryears make us believe that it has realistic effect to research deeply on the theories of the descending and ascending functions of the lung qi to guide clinical work.Based on these reasons and the earlier work, we plan to research the theories ofthe lung which loses its ascending and descending functions and to clarify itspathological basis, probe the method of recognizing the process of ALI andmechanism to treat and prevent it by using the theories of the lung qi in theCanon of Medicine, furthermore, clue the clinical meaning of using basictheories of traditional Chinese medicine and dredging clinical experience ofdifferent times to prevent and treat with severe complication of acute respiratoryinfection and to bring down its death rate and latter diseases.2. Research method2.1 Research method of theoriesOn the basis of arranging and analyzing the literature of the descending andclearing functions of the lung, combing the text of Basic theories of TCM atpresent, we identified the concept, meaning and functional characteristics of thedescending and clearing functions of the lung and clarified the mechanism of thelung which loses its descending and clearing functions combing the clinicalexperience. Meanwhile, on the basis of arranging and researching on the relatedTCM and western medicine literatures, we set up the TCM and western medicinemechanism of ALI, and according to the theories of differentiating the syndromeand treatment, we clarified the basis of the method of exorcizing the phlegm andwater and its clinical guiding meaning.2.2 Experimental research methodWe try to choose to copy the ALI mice models induced by LPS to observe thesuper-micro pathological change of organization, lung weight moisture, BloodGas Analyze and TNF-a, IL-4, PMN cell count in the BALF, thus to discuss theeffect of Zhang zhongjing's formula of exorcizing phlegm and water on ALI.2.2.1 To make the mice model of ALIEndotoxin is the LPS of the cell wall of Gram Negative Bacilli, vein injectionand trachea aspiration are the good ways to simulate ALL What we researched is ALIcaused by acute upper respiratory infection, the process of the disease and thepathological change coincide with it, so we chose ALI model induced bylipopolysaccharide LPS. According to literature method, we used tail vein injectionmethod to inject lipopolysaccharide LPS to copy ALI mice model, after injured, PaO₂of the model team began to descend, the volume of lung obviously expanded, big andsmall dark red plaques could be seen on the surface of the lung. Observed through optical Microscope, amounts of inflammatory cells exposure could be seen, also,dropsy could be seen in the alveolar and pulmonary, lung hemorrhage was obvious,and this proved that the model was successful.2.1.2 Determination of Examination target and examination method1) General condition observation: including big mice' outward appearance, theactivity, food eating, the drinking, the feces and urine, hair, the breath frequency andscope, the respiratory tract secretion, the body weight of each group before and afterthe model-making.2) Blood gas analysis: After the animal has been anaesthetized, instantly picks theblood from abdomen aorta and examines with the entire automatic blood vigoranalyzer.3). Calculation of lung wet/dry weight ratios: Weight moisture of the lung: afterthe animal was killed, choose the upper part of the right lung, weighs it, and thendry it for 24 hours, then weighs it again and calculate the wet/dry weight ratios ofthe lung.4) Observation of the pathological change of the lung organization: use paraffinsection method to entrap the lung organization, dye with HE method, and observewith optical microscope.5) Super-micro structure change observation: use Glutaral and Osmic acid to stablethe organization and use TEM to observe the super-micro change of the lungorganization.6) Counting of BALF PMN: use Jurgens Staining Method to count the amount ofwhite ceils and Giemsa Staining Method to count the cells.7) Determination of TNF-a: RIA method to determine TNF-a.8) Determination of IL-4: RIA method to determine IL-4.3. Results:3.1 Theory research results:Combine with the literature material and after analyzing and discussing onthe essence of the descending and clearing functions of the lung and the clinicalsymptoms of the lung which loses its descending and clearing functions, wemake the following conclusions on it:1). Dysfunction of the descending and clearing functions of the lung is thepathological basis of immanent obstruction and restriction lung diseases. This isbecause the descending and clearing functions of the lung is the basiccharacteristics of the activities of the lung qi under the physiological condition and also the basis of all the physiological activities of the lung.2). According to the clinical manifestation of ALI, We realize the correlationbetween dysfunction of the descending and clearing functions of the lung anddevelopment of ALI.3). Phlegm is the key mechanism of the lung when it loses its descending andclearing functions and it acts an important role in the process when the lung losesits descending and clearing functions. Phlegm is the basic and most importantpathological change of the respiratory system diseases. It is not only thepathological product of the body, but also one of the most important factors tocause diseases. According to the etiology and mechanism theories of TCM, nomatter what diseases produce phlegm, or the phlegm cause diseases, phlegm isthe combination of the primary etiology and secondary pathological product, andbecomes an important factor to cause diseases.4). ALI/ARDS coincides with the symptoms of "Jiexiong" of TCM, the mainpathological characteristics of ALI/ARDS is the formation of pulmonary edema andtransparent membrane which contains abundant protein in the alveolar exudationcaused by the high permeability of the lung micro-vessel and combine with thepulmonary fibrosis. All these exudates and sub-eschar tissue fluid stay in the gaps ofthe lung organization and form the phlegm of TCM. So, we think that the pathologicalbasis of ALI is because the lung loses its descending and clearing functions, and thephlegm stays in the chest is the key mechanism. Therefore, to exorcizing the phlegmand make the movement of lung qi normal is the key method to deal with ALI, this isthe combination of TCM theories and clinical experience and is the importantexperience to deal with ARDS. So, we decide to choose the method of exorcizing thephlegm and water to deal with the ALI mice induced by endotoxin.3.2 Experimental research results:1). After the model has been made, the mice appeared the followingcharacteristics: the hair erect and lose gloss, easy to be frightened, dietingdecrease, dry stools, after taking Chinese herbs, the stools becomes loose andstool frequency increases, breath frequency increases after injecting LPS, pinkexcrete fluid from the nose, but the second day after the model was made, thebreath frequency of the mice in each team decreased.Lung moisture became higher obviously after the model was made, model team ishigher than that of treating team, and treating team is higher than that of blankteam, there are obvious differences between each team.(p＜0.05)。 2). Blood gas analysis: PaO₂ of the model team is obviously lower than that ofother teams (p＜0.01), no differences exist between the treating team and blank team,both of them are in the normal range.3). Weight moisture of the lung: after the animal was killed, choose the upperpart of the right lung, weighs it, and then dry it for 24 hours, then weighs it andcalculate the moisture of the lung.4). Pathological changes of the lung organization of each team: the micro-vessel of thelung of the mice in the model team expanded obviously and obvious congestionformed, amounts of inflammatory cells infiltrated in the pulmonary, parts of thealveolar were filled with exudation, transparent membranes formed, changes of thepathological characteristics in each treating teams are lighter than that of the modelteam, alveolar in the blank team has no exudation observed with optic microscope,little of inflammatory cells infiltrated in the pulmonary, no micro-vessel congestedand expanded in the pulmonary.5). Super-micro structure change observation: observed with TEM, we found thatâ… cells of the alveolar in the model team was intumescent, the core of some of the cellsbroken,â…¡cells of the alveolar appeared LB caving, and ceils intumescence,meanwhile, basilar membrane thickened, micro-vessel became weak and congested.The Changes of alveolar cells in each Treating teams was not obvious, but basilarmembrane thickened, micro-vessel became weak and congested. No changesappeared in the alveolar, basilar membrane and micro-vessel in the blank team.6). Counting of BALF white cells and PMN: counting of white cells is obviouslylower in the treating teams than that of the model team(p＜0.05), compared withblank team, no obvious difference (p＞0.05), counting of white cells is obviouslyhigher in the model team than that of the blank team(p＜0.05). PMN cells countingresult is that the model team is obviously higher than that of other teams(p＜0.05).7). Determination of TNF-a: TNF in the model team is higher than that of treatingteam, and treating team higher than that of blank team (p＜0.05).8). Determination of IL-4:IL-4 in the model team is higher than that of treatingteam, and treating team higher than that of blank team (p＜0.05).4. Conclusions1). ALI/ARDS correlated with dysfunction of the descending and clearingfunctions of the lung. Impairment of clearing and descending function of the lung isthe pathological basis of ALI, and the phlegm stays in the chest is the key mechanism. 2). Formulas of exorcizing the phlegm and water can protect the lungorganization of ALI, and can relieve the pathological injury of the lung and theedema. It can obviously relieve TNF-a and the gathering of inflammatory ceils inthe lung organization, which proved that it can relieve the symptoms of ALl by lowerthe TNF-a and PMN. Meanwhile, it can restrict and protect the over-inflammatoryreaction, so, its effect mechanism probably exists in make the balance of adjustinginflammation and anti-inflammation. But, if it is effective to anti-inflammation factorsor inflammation factors has not been researched. But further research could beconsidered in the future.3). To deal with diseases such as pulmonary emphysema, chronic pneumocardialdisease, Lobar Pneumonia and acute lung injury in TCM clinics, we can not only usethe method of descending and clearing the lung qi, but also the method of treat withphlegm. In the TCM clinics, when deal with the related diseases caused by upperrespiratory infection, such as acute lung injury, which has the main pathologicalcharacteristics of loses its descending and clearing function, we can choose themethod of exorcizing phlegm and water and recover the stools, thus to make thephlegm excreted and protect the lung qi. This method represents the basic experienceof TCM to deal with respiratory system diseases since Zhang zhongjing's time.4). TCM and western medicine are the two different systems, the lung in theZangxiang theories of TCM can not be simply equaled to that of western medicine. So,in TCM clinics, when deal with lung system disease, we must focus on the integrationviews and the method of differentiating and treating syndromes according to Zangfutheories of TCM, which need to differentiate the exterior and interior, deficiency andexcess, cold and heat, but not just deal with bacteria or virus and just use the methodof dealing with inflammation and virus.5. Creativity1). Systematically clarified the key pathological mechanism of the lung when it losesits descending and clearing functions and specially mentioned the relationshipbetween the phlegm and it, thus, supply theoretical basis for using the method ofexorcizing phlegm and water to treat with ALI.2). From the research, we expand the idea of how to carry out the study ondysfunction of the descending and clearing functions of the lung, and find a newentry point that some classical empirical Chinese medical formula will be used to treatALI/ARDS.3). Using strong exorcizing and warm exorcizing method for the first time and discussed the effect and mechanism of TCM to deal with ALI and ARDS from thesphere of RIA, pathology and micro-structure, thus did important basic research forTCM to participate in dealing with acute severe respiratory system diseases andsupplied material for the coming clinical job.