Experimental Research Of Mechanisms On Rabbit Model Of Initial Cor Pulmonale Treated By Decoction Of Replenishing Lungs And Activating Blood Circulation

I The guiding theory of designing experiment and selecting test indicators:three-dimension-macro-trend theory1Three-dimension-macro-trend theoryAny life only has the life dimensions of matter, energy, space-time, and the life is a course of self-serving,self-cleaning and self-smoothening. With the three dimensions of matter,energy, and space-time, the human life is the dynamic process of material and energy intake, storage, use and discharge first and foremost. The body has formed a set of improved immune mechanism in the long run of evolution which shows the macro-immune-trend (or law) in the macro perspective to drive out the substances that are not conducive to the body and that include harmful physical and chemical substances,bacteria,viruses and other pathogenic micro organisms, excessive normal life needs or accumulation of physical products from the body. Body has the following five basic macro trends to drive out the pathogenic factors or minimize the damages.First, where out is just the one in because the place coming from is where easy to go out.Second, the pathogenic factors are drived out from the nearest or the most convenient large body cavity linking the outside. Third, they are drived out through fistula developed by the nearest path to the surface. Fourth, the paths are the micro ones. Fifth, they are beleaguered where they develop. But driving-out is always ultimate of the human macro-immune-trend.The body's macro-immune trend show in the disease's occurrence, development and transfer process,and in the same time, the changes of healthy minarals and energy and the pathogenic factors are also demonstrated through matter dimension (by strongth or weakness of healthy minarals and energy and the pathogenic factors),the energy dimension(by temperature and the heat or cold feeling),spatial dimension (by disease location).so the overall fighting trend between them appears.From the inherent three life dimensions of human body, Chinese Medicine describs the macro trend of human physiological and pathological laws and phenomena, and describs all healthy minerals and functions as Zhengqi and the pathogenic factors as Xieqi by dichotomy. The general therapy principle is set out based on struggling trend between them that is three-dimension correction, strenthening Zhengqi and driving out pathogenic factors according to the trend of Zhengqi frighting Xieqi.Traditional Chinese Medicine is three-dimension-macro-trend medicine which cures diseases according to the trend of Zhengqi frighting Xieqi and by correctting abnormalities of life three dimensions. Traditional Chinese Medicine also describes the three dimensions and one trend of Chinese medicine:1)The heat or cold of the medicinethe energy dimension,2)five taste-matter dimension(components),3) the target meridians and collaterals of Chinese medicine (specific tissues,organs,namely, the space selective role)theory-space dimension,4) lift ups and downs(4 gases)--the macro-trend of movement direction. The general principle of Chinese herbal compound is three-dimension correction, strenthening healthy minerals and energy and driving out pathogenic factors according to the trend of Zhengqi frighting Xieqi,too.2 Selecting test indicators2.1 To reflect the life three dimensions of material,energy, space-time,namely, reflect the differentiation of eight principle syndromes of Traditional Chinese Medicine.Matter dimension-all macro-and micro-indicators of specific life substances belong to the matter dimension.Energy-dimension-body temperature, ATP, ATP enzyme, the subjective hot and cold feeling,and so on.Space-time dimension-time, season, space, environment, volume, size, location and other relevant indicators and so on.2.2 To reflect the the whole or partial life moving trendThe indicators of hyperactivity, multi-language, or silence to reflect the the whole moving trend;The indicators of polydipsia,blood clotting Qi stagnation to reflect the local moving trend.2.3 To reflect the Chinese Medicine thinking to strengthen the healthy minerals and energy and driving out pathogenic factors:Strengthening healthy minerals and energy-the indicators to reflect tissues repair,functions completed or improvedDriving out pathogenic factors-the indicators to reflect the changes of internal and external pathogenic factors.Showing the trend btween the healthy minerals and energy and the pathogenic factors,and the path of pathogenic factors being drived out.The former indicators can be included in the ones of strengthening healthy minerals and energy or driving out pathogenic factors.The latter can include a lot,such as sweating, coughing out old phlegm, expeling out congestion, discharging the dry plot, etc.II Experimental researchObjective:The therapeutic mechanisms were initially reveal that the rabbit models of cor pulmonale were treated with Decoction of Replenishing Lungs and Activating Blood Circulation by the experiment under the guide of Three-dimension-macro-trend theory. The results and conclusions will become the basis to further research the Decoction and provide a thinking for sdudy of Traditional Chinese Medicine and it's medicine compound.Methods:40 average class white rabbits with big ears,purchased from the Test Farm of Shahe in Beijing,permits Lot:scxk Beijing 2005-0003,no differentiation of the male and female, about 2kg each, and they divided randomly into normal control group, model group of cor pulmonale,treatment group of Decoction of Replenishing Lungs and Activating Blood Circulation, and the captopril treatment group,10 rabbits in each group, The control group was not modeled, and the other groups were modeled altogether,and all groups were fed with the same feed.Referring to rabbit model of cor pulmonale made by Yu Qiu-tong in Zhejiang Medical University, the models were copied by injection of 0.7% ferric chloride solution from rabbit ear vein one time every other day. The modeling times were 20. From behaviors and two-dimensional echocardiography, cor pulmonale model had successed, modeling ended. After modeling,each rabbit was taken blood from the ear vein for Observation of blood macro-morphology and detection of AngⅡ,ET, TXA2/PGI2, NO, TNF-α. firstly, Control and Model group were fed only after the former method then, and China group fed with the viscose cream, West group fed with captopril,and two medicines were all given once a day. Eight rabbits survived to the end of delivery in each group, and the total was 32. Firstly, to observe and not the behavior characteristics of rabbits,and to take blood from ear vein for the observation of blood macro-morphology and extraction of plasma or serum, for the same detection indicators at the end of modeling, then to kill the rabbits for observation of general hear tand lung morphological characteristics and derive rabbit lung tissues to make the heart and lung biopsy, detection of lung cell proliferation and apoptosis and the changes in ATP enzyme activity.Results:PartⅠ:From the difference of general morphology, the color,xcrescences of heart and lungs,and the changes between heart and it's pericardium, a good efficacy has shown in Decoction of Replenishing Lungs and Activating Blood. The efficacy also was proved by the micro-morphological changes in cardiac muscle, pulmonary artery, thrombosis and behavors of inflammatory cellsPartⅡ:By analysis of variance and q test of vasoactive factors AngⅡ,ET, TXA2/PGI2,NO, and inflammatory cytokine TNF-α,conclusions are as follows:Decoction of Replenishing Lungs and Activating Blood Circulation can very significantly improve the serum NO levels (p<0.01);and has the trend to lower blood Ang II,ET and TXA2/PGI2, and has no effect to TNF-α,and no significant difference on TNF-αappear between th ebefore and after treatment and among the four groups after treatment.PartⅢ:Decoction of Replenishing Lungs and Activating Blood Circulation has significant effect in promoting cell proliferation in lung tissue (p<0.05),and apoptosis is not observed in each group.PartⅣ:Decoction of Replenishing Lung and Activating Blood Circulation can improve markedly Na+-K+-ATP enzyme activity of lung tissue (p<0.01),and has no significant effect to Ca2+-Mg2+-ATP enzyme activity.Analysis of results:Despite cor pulmonale can show many syndromes,the deficiency of lung-Qi(and Yang)and blood stasis of lung are the main and common pathophysiological features;and replenishing Qi (and Yang) of lung and activating blood circulation are a general thinking and main methods for Traditional Chinese Medicine to treat cor pulmonale. Decoction of Replenishing Lungs and Activating Blood Circulation was a clinical prescription of Traditional Chinese Medicine created by Academy Dong jian-hua for the people with chronic cor pulmonale which was created on the basis of Decoction for Reinforcing Middle-warmer and Replenishing Qi and Decoction for Dissipating Blood Stasis in Chest,and in which Astragalus,Lu Codonopsis,White Atractylodes Rhizome and Licorice can reinforce Qi of spleen and lungs;Bupleurum, the Peel of Bitter Orange,Balloonflower Boot and Dried Old Orange Peelcan can regulate the flow of Qi contribute the ascending trend of lungs and spleen; Chuanxiong Rhizome,Bidentata, Angelica Sinensis,Peach Kernel,Safflower and Red peony Root can promote blood circulation and dissipate blood stasis;Dried Rehmannia Root can nourish Yin and body fluid. Just from thecold or hot nature of the herb, Astragalus is slightly warm; White Atractylodes Rhizome, the Peel of Bitter Orange,Dried Old Orange Peel,Chuanxiong Rhizome, Angelica Sinensis and Safflower are warm; Lu Codonopsis,Balloonflower, Licorice, Peach Kernel and Bidentata are bland; Red peony Root and Bupleurum are slightly cold; Dried Rehmannia Root is cold. The quatity proportion of the slightly warm, the warm,the bland, the slightly cold and the cold is 10/42/40/11/9.The prescription has prominently warm nature and the effect of reinforcing Qi and warming Yang and activating blood circulation, and warming Yang is most important.The experimental results show that the increase in Na+-K+-ATP enzyme activity may be one of the mechanisms that cor pulmonale was treated by Decoction of Replenishing Lung and Activating Blood Circulation which was created on the thinking of reinforcing Qi and warming Yang and activating blood circulation.Conclusion:The experiment primarily revealed the treatment mechanisms of Decoction of Replenishing Lungs and Activating Blood Circulation,namely the way of YiQi,WenYang and Activating Blood Circulation to cor pulmonale, from the angle of tissue repair (promotion of cell proliferation in lung tissues),energy metabolism (enhanceing lung tissue na+k+ATP enzyme activity), vasoactive substances(increase in vascular relaxing factor NO content),anti-inflammatory effect and the side-effect(No significant differences are in TNF-αlevel between the before and after treatment and among the four groups after treatment).The experiment also denies initially the most undesirable side-effect.Selection of experimental indicators is also fully reflected the Decoction's efficacy of strengthening healthy minerals and energy (promoting lung tissue cell proliferation, and enhancing lung tissue na+k+ATP enzyme activity),correctting the pathological situation(regulating vasoactive factors on dilation and contraction, the dissipation of thrombosis, reducing blood viscosity, etc.),and the test of Driving out pathogenic factors and sade effects (TNF%αdetection).T(e effiaacy of The Decgct)g, aA bEef profed objective, beine worthy of further study.