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Chronic Obstructive Pulmonary Disease Rat Model, Pulmonary Disease And Intestinal Experimental Observations

Posted on:2012-11-16Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y WangFull Text:PDF
GTID:1114330335458969Subject:TCM clinical basis
Abstract/Summary:PDF Full Text Request
Originated from "Huangdi Neijing", the Lung Being Relative to the Large Intestine Theory reflects the Holistic view of Chinese Medicine. On one hand, the Theory has been used to treat Respiratory diseases such as COPD, ARDS, Pulmonary heart disease, Bronchial asthma, cough, etc. On the other hand, it also has been used to treat digestive system-related diseases like Constipation, Peptic ulcer and Chronic enteritis. As a specific form of the Lung Being Relative to the Large Intestine Theory, "Enteropathy caused by lung disease" can confirm the Theory to some extent, and furthermore to provide some important evidences to reveal the meaning of the Theory.Clinical data shows that other than respiratory symptoms, COPD usually accompanied by gastrointestinal symptoms such as abdominal distension and constipation. Treatments of COPD based on Chinese Medicine not only can relief symptoms during acute period, but also can reduce the incidence and mortality, and improve the quality of life as well. In spite of its significant effects on COPD, the mechanisms of the Chinese Medicine treatments have not been very clear yet.Based on literature research, this paper designed three experiments on "Enteropathy caused by lung disease" in COPD. Through observing morphologic alterations and the effects of the modified Jiegeng Decoction on rats with COPD, and detecting Neuropeptide contents in different tissues of rats with COPD, analyzed and clarified the features of "Enteropathy caused by lung disease" step by step. The paper consists of three parts:Part one is reviews. It reviewed systematically on the research survey of the Lung Being Relative to the Large Intestine Theory and advances in studies on COPD.Part two is theoretical explorations. It straightened out the Mechanisms of COPD based on TCM, and analyzed the Strategy of TCM syndrome differentiation and treatment of COPD.From TCM's point of view, the basic pathogenesis of COPD is essential debility and evil reality. Essential debility means lung, spleen and kidney deficiency. Evil reality means wind-evil, cold-evil, dampness, phlegm and stasis. So the treatment of COPD should adhere firmly to this basic mechanism and take into account other factors at the same time.In "Shang Han Lun", the formulas which treating cough and asthma all reflect the discipline of taking into account of both exterior and interior, cold and heat, reinforcement and elimination, and show the principle of treating in terms of root cause as well. The formulas scattered in several sections in "Shang Han Lun" which reveals the observation of the process of cough and asthma.Part three is experimental study. Observed the alternations of morphology in rats with COPD to confirm that there is a phenomenon of "Enteropathy caused by lung disease" in COPD, and validated the phenomenon through exploring the mechanism of the therapeutic effect of modified Jiegeng Decoction via inflammatory cell and cytokine. Observed the influence of facilitating lung on contents of NKA and VIP in lung tissues in rats with COPD, and investigated the mechanism.Experiment one:COPD rat model was induced by cigarette smoking inhalation and intratracheal LPS exposure. Rats were divided into 4 groups, namely normal group, model group, model treating group, normal treating group. Normal group and model group were given saline, other groups were given modified Jiegeng Decoction from the 2nd day to 13th day and the 15th day to 28th day. Took lung, intestine, heart, liver and kidney tissues of rats, made specimen for optical microscope. Results showed:①The light-microscope observation show that in the model group, the structure of bronchoalveolus is destructive, detelectasis and the interval is broaden, coalesce. There were many inflammatory cells infiltration in alveolar wall. These pathological changes indicated the rats had COPD.②The range of pathological changes in model treating group reduced and the infiltration of inflammatory cell decreased obviously, indicated that modified Jiegeng Decoction can relief the degree of inflammation in lung tissue.③In the intestine tissues of model group, inflammatory cell infiltration in the epithelium, submucosa irregularly arranged, indicated the COPD model rats had pathological changes of intestine tissue.④The inflammatory cell infiltration in intestine tissues of model treating group decreased indicated modified Jiegeng Decoction can ease the lesions of intestine.⑤there was no significant histology damage in the tissues of heart, liver and kidney, indicated COPD injures intestine more seriously.Experiment two:Measured the content of TNF-a, IL-1βwith the ABC-ELISA method and observed the body weights and the intestine propulsive motilities of the rats. Results showed:①Compare with normal group, the amount of lymphocytes and the content of TNF-a and IL-1βof model group increased significantly. It showed that the model group had the sign of inflammation.②The amount of lymphocytes and the content of TNF-a and IL-1βof model group decreased obviously, showed the inflammation in airway relieved.On the other hand, the results of the body weight and the intestine propulsive motility showed①Compare with normal group, the body weight and the intestine propulsive motility of model group decreased significantly, indicated COPD can inhibits the gastrointestinal motility and impacts nutritional status.②The body weight and the intestine propulsive motility of model treating group increased obviously, indicated modified Jiegeng Decoction can improve the gastrointestinal motility and impacts nutritional status.From the analysis of pharmacodynamic index test, modified Jiegeng Decoction not only controled the inflammation in airway, but also improved the gastrointestinal motility and impacts nutritional status. That is to say, treating COPD from lung can inhibit the pathological changes in lung tissues and at the same time ease the pathological changes in intestine tissue.Experiment three:Took lung, intestine, heart, liver and kidney tissues of every group rats, measured the content of VIP and NKA in the tissues with radio-immunity methods. The results showed:③Compare with normal group, the amount of NKA in lung and intestine tissues of model group increased while the amount of VIP decreased, especially in lung tissues, indicated COPD can change the amount of NKA and VIP both in lung and intestine which is related with "Enteropathy caused by lung disease",②The amount of NKA in lung and intestine tissues of model treating group decreased while the amount of VIP increased, indicated modified Jiegeng Decoction can regulate the changes of NKA and VIP in lung and intestine which induced by COPD.③The results of the correlation analysis between the amount of NKA and VIP in lung tissue and the amount of TNF-a and IL-1βin BALF indicated the effect of modified Jiegeng Decoction may be related with its regulation of NKA and VIP in lung tissue.④The amount of NKA and VIP in other organ tissues did not change significantly, indicated the impact of COPD on the amount of NKA and VIP is most obvious in lung and intestine.⑤The results of the correlation analysis between the amount of NKA and VIP in lung and intestine showed, the changes in lung synchronized with the changes in intestine. The regulation of modified Jiegeng Decoction on the gastrointestinal motility and nutritional status may be related with its impact on the amounts of NKA and VIP in lung and intestine.Conclusion:Rats with cigarette smoke and LPS-induced COPD have lesions of lung tissue accompanied by pathological changes of intestine tissue. Therefore, cigarette smoke and LPS-induced COPD rats have "Enteropathy caused by lung disease".Treating COPD model rats with modified Jiegeng Decoction can reduce the inflammation in airway and improve the gastrointestinal motility and nutritional status. It indicates treating from lung can also relive the pathological changes of intestine.The therapeutic effect of modified Jiegeng Decoction may be related with its regulation of the amounts of NKA and VIP in lung and intestine which need further research.
Keywords/Search Tags:"Enteropathy caused by lung disease", COPD, Inflammation, NKA, VIP
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