| Objective1.To introduce academic thoughts and clinical experiences of Prof. Sun Zhijia on treatment of chronic obstructive pulmonary disease(COPD).2. To observe the effects of reinforcing earth to strengthen metal on the weight, lung and diaphragm tissue morphology, and the proliferation and apoptosis of the diaphragmatic cell in rats with COPD. Trying to approach the effect of reinforcing earth to strengthen metal on the aspects of the pathway of diaphragmatic cell apoptosis and the pathway of nuclear factor-kB to research the influence and the mechanism of the TCM treatment on diaphragmatic fatigue to provide a scientific basis guiding clinical medication of improving the condition of patients with COPD.Methods1. Through a variety of ways to systematically collect, read Professor Sun Zhijia published over the years and unpublished papers, lecture notes, clinical experience, as well as the process of consultation with Professor Sun’s collection of clinical experience and proven Herbal Prescription, summarized Professor Sun Zhijia’s dialectical thinking and clinical experiences in the treatment of COPD.2. The rat model of COPD was established by intratracheal instillation of lipopolysaccharide(LPS) and exposure to cigarette smoking. Forty Wistar rats were randomly divided into normal group(NG), model group(MG) Chinese medicine high dose group(HDG) and low dose group(LDG). The overall situation and the weight of rats were observed. Pathologic changes of lung and diaphragm tissues and the dynamic blood gas analysis were studied to evaluate the protecting effect of reinforcing earth to strengthen metal on COPD rats.3. Immunohistochemistry was carried out to detect the content of PCNA protein to calculate the proliferate index(PI) of proliferate cells, and terminaldeoxynucleotidyltransferase-mediated dUTP nick end labeling methods(TUNEL) was carried out to examine the apoptotic cells to calculate the apoptotic index (AI) and the percentage of PI/AI in diaphragm tissues, which can assess the effect of reinforcing earth to strengthen metal on keeping balance between proliferate and apoptotic process in diaphragm of COPD rats.4. Immunohistochemistry was carried out to detect the content of Fas,FasL, Bax, Bcl-2, and P65 protein, as well as RT-PCR was carried out to detect the expression of P65 mRNA in diaphragm tissues of COPD rats. Trying to explore the mechanism of reinforcing earth to strengthen metal in the pathway of diaphragmatic cell apoptosis and the pathway of nuclear factor-kB.Results1. Academic throughts of Professor Sun Zhi jia can be summarized as 3 points: to identify the deficiency and excess of actual situation to cure the disease, to detect stage and the location of the disease in the viscera and to pay attention to the constitution to prevent the disease from deteriorating. Clinical application on the basis of strengthening earth to generate metal as well as other principles such as:treatment by different stages and syndrome, pay attention to the pathologic results-Phlegm, heat, blood stasis and deficiency of patients, Dialectical medication, don’t rule out strong medicine, emotional regulation combined with dietary counseling and physical exercise.2. COPD rat bronchial lung tissues under the appearance and light microscope present shuch changes as emphysema and airway inflammation. This TCM formula can obviously improve the pathological changes of the pulmonary emphysema and airway inflammation.3. The weight and PO2 in arterial blood in MG were significantly lower than NG, PCO2 in arterial blood was higher than NG. This TCM formula can increase the content of PO2 and decrease the content of PCO2.4. Compared with NG, the percentage of apoptotic cell of diaphragm in MG was significantly higher than those in NG, and the ratio of proliferative index/apoptotic index (PI/AI) of diaphragm tissue cells in MG was significantly lower than that in NG. Compared with MG, the weight of HDG increased significantly, the percentage of apoptotic cell was significantly lower than those in MG, and The ratio of proliferative index/apoptotic index(PI/AI) of diaphragm tissue cells in HDG was significantly higher than that in MG.5. The protein expression of Fas, FasL, Bax and P65 in MG, HDG and LDG were all higher than those in NG, the protein expression of Bcl-2 was contrary to the result. And the protein expression of Fas, FasL, Bax, P65 in HDG was lower than that in MG. As well as, the protein expression of Bcl-2 was higher than that in MG. The P65 mRNA gene expression was no statistical significant in all the groups.Conelusion1. Professor Sun Zhijia summarized that:in the pathogenesis of COPD, the difieieney of the lung due to protracted disease is the basis of morbidity; exogenous evil is the important inducement; stagnation of phlegm-heat is the key reason of acute recurrence; blood stasis and phlegm are always runs through the disease. The disease of COPD attacks the lung first, then pass to the spleen, finally to kidney, heart, brain and other organs. He also pay attention to the constitution, which may be the determinant of the outcome of disease. Professor Sun Zhijia treats COPD based on some principles as follows:to identify the deficiency and excess of actual situation to cure the disease, to distinguish the pathological factors, to detect stage and the location of the disease in the viscera. He thinks that we should eliminate pathogen that stagnant phlegm when the disease is the period of acute exacerbation, and reinforce lung, spleen and kindey while catabasis, especially the spleen, and when eliminating pathogen, don’t forget strengthening body resistance, vice versa. Don’t rule out strong medicine, emotional counseling combined with diet-control and physical exercise are also important therapy paied attention.2. TCM formula:reinforcing earth to generate metal for play a protective role in lung and diaphragm tissues injury of COPD rats, increase the weight, relieve the symptoms and improve the general condition of COPD rats.3. TCM formula:reinforcing earth to generate metal can effectively improve hypoxemia and hypercapnia of COPD rats to enhance the function of lung ventilation and the respiratory function.4. TCM formula:reinforcing earth to generate metal can inhibit the expression of protein in diaphragm tissues related to apoptosis pathway s-Fas/FasL death receptor pathway and mitochondrial pathway, decrease the apoptosis, and keep balance between apoptosis and proliferation process of diaphragm tissue cells, which may be involved in treatment of improving the respiratory function and alleviating diaphragmatic fatigue in COPD.5. TCM formula:reinforcing earth to generate metal can inhibit the expression of NF-κ B P65 protein in diaphragm tissues related to NF-κ B pathway to induce the decrease of apoptosis of diaphragm tissue cells, not by increasing the expression of NF-κ B P65 mRNA to cause the corresponding cell apoptosis effect. |
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