| ObjectiveAs the impact of environmental issues and other factors, respiratory diseases have paid increasingly much attention. In recent years, idiopathic pulmonary fibrosis (Idiopathic Pulmonary Fibrosis, IPF) disease has become a hot research. Theory research:Using "Yellow Emperor" theory, to disscuss the theory of Zhongjing Treating lung disease and drug laws, and the relationship between the consumptive or paralysis lung disease and pulmonary fibrosis, it aimed at exploring the ancient experience in the treatment of lung disease, and implications for the treatment of pulmonary fibrosis disease. Experimental research:To study the prevention and treatment of Idiopathic pulmonary fibrosis, using different administration programs was aimed at finding the best Nourishing Yin Clearing Heat and Resolving Phlegm, Nourishing Yin Supplementing Qi and Activating Blood sequential treatment regimen of prevention and treatment of Idiopathic pulmonary fibrosis, and initially exploring the molecular mechanism to provide scientific basis for the treatment of IPF.MethodsTheory research:Using "Yellow Emperor" theory, summarizing the discussion of lung disease in the "Golden Chamber", summarized the theory Zhongjing treatment and the drug laws of lung disease, integrating the discussion of consumptive lung and lung paralysis in "Golden Chamber", "Yellow Emperor" and later doctors' discussion, combined with modern researches, summarized causes, symptoms and course of lung paralysis and pulmonary fibrosis disease, exploring the relationship between consumptive lung, lung paralysis and pulmonary fibrosis, and Implications for the treatment of disease on pulmonary fibrosis.Experimental research:Animal model and administration method:105 male ICR mice were randomly divided into 7 groups, Group 1:control group, Group 2:the model group, Group 3:Western medicine group (Methylprednisolone group),Group 4:No.1 prescript for 21 days, Group 5:No.2 prescript for 21 days, Group 6:No.1 prescript 7 days before, No.2 prescript for 14 days after, group 7:No.1 prescript for 14 days before, No.2 prescript for 7 days after, (No.l prescript:Radix Ophiopogonis, Radix Scutellariae, Rhizoma Pinelliae, Radix Platycodonis= 1:1:1:1; No.2 prescript:Radix Ophiopogonis, Radix Astragali, Radix Angelicae sinensis, Radix Platycodonis=1:1:1:1) except to the normal control group, the other groups inject bleomycin via trachea, causing IPF model. After modeling the next day, five treatment groups administered according to different dosing regimens for 21 days, the mice were recorded and observed the survival or death state, after 21 days,taked the lung tissue, serum for standby. Then proceed to the following experiments.Experiment 1:The survival status and lung morphology influence of sequential therapy of Nourishing Yin Clearing Heat and Resolving Phlegm, Nourishing Yin Supplementing Qi and Activating Blood for IPF mice. Experimental Method:Mortality curve was depicted.The statistics of changes in body weight of mice was made. IPF lung tissue morphological changes were observed by HE staining and aniline blue staining.Experiment 2:The influence of lung collagen expression in sequential therapy of Nourishing Yin Clearing Heat and Resolving Phlegm, Nourishing Yin Supplementing Qi and Activating Blood for IPF mice. Experimental Method:Using alkaline hydrolysis method, hydroxyproline content of IPF lung tissue homogenates was measured; Using RT-PCR assay method, type ?, ? type, ? type, ? collagen gene expression levels in lung tissue were detected.Experiment 3:The influence of IL-6, TGF-? expression in sequential therapy of Nourishing Yin Clearing Heat and Resolving Phlegm, Nourishing Yin Supplementing Qi and Activating Blood for IPF mice. Experimental Method:By using ELISA method, the content of IL-6, TGF-? in serum was measured; Using RT-PCR assay method, IL-6, TGF-? gene expression levels in lung tissue were detected.ResultsTheoretical Study:1 In treating ideas, lawed of heaven and earth, and used laws of the water's lifting and gasification between heaven and earth to the lift and down in the human lung and stomach gasification. If consumptive lung because of asthenia-cold, Yang of spleen-earth should be excited, up to nourishing the lung, If consumptive lung because of asthenic heat, Yin of spleen and stomach should be nourished up to water of lungs, if lung abscess because of excess heat, removing water by bitter and cold drugs, falling down lung's water, freeing yang and promoting qi transformation if water was no transfer to metaplasia; If evil drink stayed, medication should match Lifting and lowering each other, scattering and closing each other; Lung and stomach meridians in terms of anatomy is also closely related. Lung and stomach treating together, and always protecting the Stomach Oi were also major features of Zhongjing treating lung disease. Among them, characteristics of raising lung's Oi, nourishing lung's Yin, disinhibiting water and phlegm had opened up ideas of drug therapy for the treatment of pulmonary fibrosis.2 Consumptive lung is wasting disease, pulmonary fibrosis also show the deficiency symptoms, benefiting qi and nourishing yin, warming yang and benefiting qi, removing phlegm and disinhibiting water, and other treatment of drinking laws, for treatment of pulmonary fibrosis have reference significance; Through the discussion of lung paralysis in "Yellow Emperor", combining with modern research on pulmonary fibrosis. by the causes of view, as " pant and weakness " the representative in "Yellow Emperor", lung paralysis is not entirely excess disease, but is deficient root and excessive superficial. It is because physically weak resulting in stepped evil, long depression to paralysis, which agree most physicians' considering that modern-minded pulmonary fibrosis is deficient root and excessive superficial disease; Judging from the symptoms and course of the summary view, paralysis and pulmonary fibrosis are very similar considering that the pulmonary fibrosis attributed to the lung paralysis Treating is more accurate. Ancient physicians related lung paralysis discussion has great reference value to pulmonary fibrosis, and the therapies are also worth learning.Experimental research:Experiment 1:The treatment in each group could have some help to improve the survival rate of mice, but the difference between treating groups for mortality was not significant. Western treatment mice were less thin, in treatment groups were in better condition. Pathological display that in the 6th group, alveolar tissue were significantly improved, collagen fibers were significantly reduced, inflammatory exudate relatively were smaller alveolar structures had been recovered, the 6th group treatment effect was most obvious.Experiment 2:HYP content results showed that the model group> Group 4> Group 7> Group 5> western group=6> control group, from statistical point view, the results of 6th group were more significant. According to each of the collagen gene expression level, compared with the control group, model group of type ?, ?, ?, ?type collagen of gene expression levels had increased, it may be one cause of lung collagen content final rising. Treatment group could significantly lower lung type ?, ? collagen gene expression levels, methylprednisolone medicine could lower lung ? collagen gene significantly, but Type ? was not obvious. Methylprednisolone, Chinese medicine group 4,5 could significantly inhibit the lung tissue ?, ? collagen gene expression and inhibition degree of 6 group 7 group were not obvious, and the degree of expression was proximity with the control group, it is possible that sequential was therapy more favorable in remodeling of alveolar tissue structure.Experiment 3:The effect in total serum IL-6 levels of each treatment group was little, sequential therapy group (Group 6, Group 7) could promote gene expression of EL-6, might have relationship with promoting lung tissue repair and suppress fiber. Group 6 could inhibit serum TGF-?content and TGF-?gene expression in lung, thereby inhibiting pulmonary fibrosis. Other treatment groups for lung TGF-? gene expression significantly inhibited, but the inhibition of TGF-?content in serum was not obvious.CconclusionsTheory research:1 Characteristic of Zhongjing Treating lung disease:Focusing on the relationship between lung and stomach lifting and lowering each other, Intergeneration and transforming used laws of the water's lifting and gasification between heaven and earth to the lift and down in the human lung and stomach gasification; On medication, Lifting and lowering each other, scattering and closing consistency, and focusing on accessibility of yang. Lung and stomach treating together, and always protecting the Stomach Oi were also major features of Zhongjing treating lung disease. Among them, characteristics of raising lung's Oi, nourishing lung's Yin, disinhibiting water and phlegm had opened up ideas of drug therapy for the treatment of pulmonary fibrosis.2 Judging from related discussion view of "Yellow Emperor" and "Treatise on Febrile Diseases", we consider that the pulmonary fibrosis attributed to the lung paralysis Treating is more accurate. Thus, Ancient physicians'discussion related to lung paralysis has great reference value to pulmonary fibrosis, and the therapies are also worth learning. But in the dialectical therapy, the treatment method and experience of consumptive lung related to tonifying deficiency and warming yang nourishing yin and benefiting have also important clinical value.Experimental research:It was best treatment of IPF that using No.1 prescript (Radix Ophiopogonis, Radix Scutellariae, Rhizoma Pinelliae, Radix Platycodonis), Nourishing Yin Clearing Heat and Resolving Phlegm, during the 7 days before, and using No.2 prescript (Radix Ophiopogonis, Radix Astragali, Radix Angelicae sinensis, Radix Platycodonis), Nourishing Yin Supplementing Qi and Activating Blood, during next 14 days. They all were not the best treatment choice that using western medicine, always a single prescript, or delayed alternating administration time points. And it was related to the promoting of lung IL-6 gene expression and inhibiting the expression of TGF-? gene and serum TGF-? content in the lungs, and inhibiting type ?, ? collagen gene expression levels but maintaining IV, V collagen gene normal expression in lung, but the exact mechanism remains to be further studied. |
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