Effects Of Respiratory Function Changes On Urine Volume In COPD Model Rats

ObjectiveAs a part of the lung function of Traditional Chinese Medicine (TCM), lung governing regulation of water passages is widely used in clinical. The research discussed the relationship between lung governing respiration and urine volume and its regulation mechanisms around the literature review, theoritic exploration and experimental studies.Methods1 Theoritic researchExplored the research progress of the lung governing regulation of water passages and analyzed the bioactivator associated with hypoxia of COPD and its adjustment on the urine volume. Studyed the expression of lung governing regulation of water passages in the Treatise on Febrile Diseases and Synopsis of Golden Chamber, interpreted the mechanism of action about dispersing lung qi and the effect of Chinese herbal medicine Platycodon grandiflorum and San Ao decoction and the mechanism of water channel protein in water metabolism.2 Experiment researchThe 60 healthy SPF Wistar rats were randomized into a normal control, a model group, a platycodon grandiflorum group and a San Ao decoction group with 15 animals in each group, using the random digital number method. Tracheal injection of lipopolysaccharide in combination with fumigation was used to establish rat model of COPD, since the 21st day to 28th day, the platycodon grandiflorum group, San Ao decoction group rats were given matching soup by gavage, and the normal model group rats were given the same amount of distilled water. The pulmonary function was detected by anires2005 analysis system after the urine volume test using metabolic cage method. Then, we observed the morphology of lung, kidney by HE staining, the protein and genetic express of AQP1 and AQP2 in kidney by immunohistochemical method and real-time fluorescent quantitative PCR (rt-pcr) method, meanwhile, we tested the content of NO, ET-1, ADH, ANP, PGE2 and Ang Ⅱ in lung, serum and kidney using enzyme-linked immunosorbent (Elisa) method.Results1 Literature and theory researchAbout the theory of lung governing regulation of water passages, the clinical research mainly concentrated in releasing lungs method to be used in treatment of water metabolic abnormalities, and linical symptoms focused on edema, urine volume change (oliguria, difficulty in urination, frequent urination, etc.), phlegm retention. The experimental study had found that there was some access between the lung and water passages. During aquaporins, the AQP1 and AQP2 had a close relationship with urine volume regulation. The lung tissue ischemia can lead to increase or reduce of some bioactivator, which part of the bioactive substances also existed in kidney tissues, or can control effect to urine volume including the NO, ET-1, ADH, ANP, PGE2 and Ang Ⅱ.Treatise on Febrile Diseases and Synopsis of Golden Chamber attached great importance to the role of lung during description and treatment of water metabolic disease. The dysfunction of dispersive and descending on lung can lead to abnormal water passage, and appeared edema, dispersive and descending, diarrhoea, heavy and pain in all fours, enuresis, and so on, however, to the water metabolic disease, such as water retention or retained morbid fluid, freeing lung-qi and eliminating damp would be used supplemently. The Chinese herbs mainly included ephedra, almond, and so on. The platycodon grandiflorum can release lungs, reduce phlegm, relieving sore throat and apocenosis, then the function of release lung was the basis of the other three functions, so the platycodon grandiflorum can be the representative Chinese herb of releasing lungs. In the San Ao prescription, ephedra played a role of release lung and dispelling cold, almond can smooth the lung and reduce phlegm and liquorice can act reconcile role, so the San Ao decoction can be the representative Chinese prescription of releasing lungs.2 Experimental research2.1 Gernaral caseThe overall situation was good in normal group rats, not seen obvious abnormity. During the smoking given, the model group rats appeared positive reaction such as accelerated respiration, aggravating abdominal breathing, sneeze, reduced activity, or cluster aggregation. The platycodon grandiflorum group and San Ao decoction group obviously got better than the model group rats in breath.2.2 Morphology of lung tissueThe lung tissue structure was integrity, bronchial and alveolar structure was clear and continuous in normal group rats. The alveolar structure was disorder, blood vessels of alveolar walls congestion was obvious in model group rats. The Platycodon grandiflorum and San Ao Tang group rats’ alveolar structure was almost normal, and blood vessels of alveolar walls congestion was not obvious2.3 Morphology of of kidney tissueThe structure of glomerular, renal tubular was almost normal in every group. 2.4 Pulmonary function testCompared with the normal group, the FVC, FEV1, FEV1/FVC% was descreased with statistically significant in COPD model group rats, the platycodon grandiflorum group rats and San Ao decoction group rats. Compared with the COPD model group rats, the FVC, FEV1, FEV1/FVC% increased with statistically significant in platycodon grandiflorum group rats and San Ao decoction group rats.2.5 Detection of urine volumeBefore building, there was on difference of urine wolume under each group rats. After the treatment, compared with normal group, the COPD model group rats 24 h urine volume decreases, the difference was statistically significant.Compared with model group,24 h urine of San Ao decoction group rats increased and the difference was statistically significant.2.6 The genetic express of renal tissue AQP1, AQP2Compared with normal group, the relative content of AQP1 mRNA, AQP2 mRNA increased in COPD model group rats, and the difference was statistically significant. Compared with COPD model group, the relative content of AQP1 mRNA, AQP2 mRNA in San Ao decoction group rats was reduced with statistically significant.2.7 The protein expression of AQP1, AQP2 in kidney tissueCompared with the normal group, the AQP1, AQP2 protein expression increased with statistically significant in COPD model group rats. Compared with the COPD model group, the AQP1, AQP2 protein expression decreased with statistically significant in San Ao decoction group rats.2.8 The content of NO, ADH, ET-1, PGE2, ANP and Ang II in lung, serum and kidney(1) NO content:compared with normal group, the lung tissue, serum and kidney tissue NO content in COPD model group rats was reduced, the difference was statistically significant. Compared with COPD model group, serum and kidney tissue NO content increased in San Ao decoction group rats, the difference was statistically significant.(2) ET-1 content:compared with normal group, serum and kidney tissues ET-1 content increased with statistically significant in COPD model group rats.(3) ADH content:compared with normal group, lung tissue, serum ADH levels rise, kidney tissues serum content is lower in COPD model group rats, and the difference was statistically significant. Compared with the COPD model group, kidney ADH levels increased in platycodon grandiflorum group rats, San Ao decoction group rats serum NO content reduced, kidney tissues NO content increased, the difference was statistically significant.(4) PGE2 content:compared with normal group, the lung tissue, serum and kidney tissue PGE2 content was reduced statistically significant in model group rats. Compared with COPD model group, serum PGE2 levels increased in platycodon grandiflorum group rats, lung tissue, serum and kidney tissue PGE2 content in San Ao decoction group rats increased, the difference was statistically significant.(5) ANP content:compared with normal group, lung tissue, serum and kidney tissue ANP content increased in COPD model group rats, the difference was statistically significant.vCompared with COPD model group, kidney tissue ANP content is lower in the platycodon grandiflorumgroup and San Ao decoction group, the difference was statistically significant.(6) AngⅡ content:compared with normal group, the COPD model group rats’ lung tissue, serum and kidney tissue AngⅡ content increased, the difference was statistically significant. Compared with COPD model group, lung tissue, serum and kidney tissue AngⅡ content was reduced with statistically significant in the platycodon grandiflorumgroup and San Ao decoction group rats.Conclusions1 There was a certain relationship between the lung governing qi and dredging and regulating water passage, the content changes of NO, ANP, ET-1, PGE2, ADH and Ang Ⅱ may participate in the processes of urine volume regulation upon respiratory function damage in the COPD model rats, which is likely to be one of the biological mechanisms of lung governing regulation of water passages.2 The Chinese herb platycodon grandiflorum, as a kind herb of releasing lung, can improve the pulmonary function and sweat gland of COPD rats, but there was no obvious improvement in urine volume and water channel of urine protein. Thus, from another angle showed the lung governing regulation of water passages was based on the dispersing and descending of lung qi.3 San Ao decoction can improve the lung function of COPD rats, at the same time, its regulating waterways function recovered, then illustrated the effect of San Ao decoction treating COPD was curative. The lung governing regulation of water passages had a close contact with lung governing breath, NO, PGE2, Ang Ⅱ, ANP and ADH may be one of intermediate link of lung upon water passages.Special features and innovation point1 Discussing the the modern biological mechanisms of lung governing regulation of water passages from the observation of bioactive substances, which provides methodology reference for the TCM viscera-state study.2 Using the techniques of morphology, immunology and molecular biology, through the animal experiments, carrying out multiple factors and levels and indicators of observational studies from the observation of bioactive substances in allusion to "lung governing the regulation of water passages", which provide experimental basis to reveal the essence of the "lung being upper source of water", clarify mechanisms of uroschesis, meanwhile, innovating and enriching the connotation of the basic theory of TCM.