| Objective:To select common Chinese traditional medicine treatment for COPD. On the basis of effective and safe therapy on COPD, we use systematic review and meta-analysis to observe the characteristics between COPD patients in Xinjiang province based on epidemiological investigation and COPD patients in other provinces based on literatures. To observe the TCM syndrome distribution characteristics of COPD in Xinjiang and find the special pattern of syndrome. On this basis, to establish Xinjiang cold-dryness animal models of COPD. To provide evidences for revealing the biological mechanism of the cold-dryness COPD and regionalized prevention and treatment for COPD.Method:To evaluate the effect and safety of Xiaoqinglongtang for treatment of COPD and TCM sticking therapy for patients with stable COPD by using systematic reviews and meta-analysis. To reveal the characteristics of COPD in Xinjiang by using TCM syndrome epidemiological investigation, then to compare characteristics of COPD between them in Xinjiang and them in other provinces based on reports in literatures. Based on the method of etiologic simulation-chronic stress-biological phenotype-pharmacal disproof, to establish the COPD models by instilling elastinase into trachea and fumigating for90days. We determined the success of model construction by observing pulmonary function, pathological change and biological phenotypes. To detect the pathophysiological change by Elisa, real-time PCR and Western-blot.Results:1. the effective rate of combing western medicine and Xiaoqinglongtang is higher than only using western medicine [MD=3.91,95%CI (2.50,6.12), P<0.00001]. The effective rate in group of Xiaoqinglongtang combined with invasive ventilation is better than simply invasive ventilation group[MD=3.48,95%CI (1.45,8.32), P=0.005]. For the improvement of PaO2western medicine combined with Xiaoqinglongtang is superior to simple western medicine[MD=7.55,95%CI (1.41,13.68), P=0.02]; For the improvement of PaCO2western medicine combined with Xiaoqinglongtang [MD=-7.11,95%CI (-9.89,-4.33), P<0.00001] and Xiaoqinglongtang combined with invasive ventilation [MD=-6.66,95%CI (-8.79,-4.54), P<0.00001] are all superior to simple western medicine. For the improvement of FEV1, western medicine combined with Xiaoqinglongtang is superior to simple western medicine [MD=6.97,95%CI (3.60,10.34), P<0.0001].2. The effective rates of COPD in the groups combined with external application are superior to the groups without external application[MD=3.63,95%CI (2.84,4.65), P<0.00001]; For improvement of FEV1, the group of western medicine combined with external application is superior to simple western medicine group. For improvement of FEV1/FVC, the group of TCM combined with external application is superior to simple TCM group [MD=5.29,95%CI (2.52,8.07),P=0.0002].3.1) The most frequent symptom of COPD in other provinces are cough (313,22.88%), sputum (204,14.91%), asthma (124,9.06%) respite (120,8.77%), shortness of breath (91,6.65%), wheeze (54,3.95%), chest tightness (45,3.29%), fatigue (40,2.93%), anorexia (38,2.78%), shortness of breath (36,2.63%), spontaneous (28,2.05%), colds (27,1.97%); The most frequent symptom of COPD in Xinjiang are shortness of breath (317,4.43%), cough (310cases,4.33%), asthma (288,4.02%) throat, dry mouth (259,3.62%), lassitude (244,3.41%), sputum (235,3.28%), chest tightness (227,3.17%), forgetfulness (226,3.16%), sweating (211,2.95%), itchy throat (207,2.89%), chills (206,2.88%), fatigue (206,2.88%). The patients with the clinical manifestations "dry"(dryness of the mouth and throat, dry nose) are259cases, accounting for63%of in total cases under investigation; patients with the " cold " manifestations (evil wind chills, shaped cold, cold back, limbs) are164cases, accounted for40%of all investigated cases., patients with both symptoms are110cases, accounting for27%of all cases under investigation. The COPD symptoms in other provinces are slip known for lung (237,59.55%), spleen (81,20.35%), kidney (74,18.59%), disease nature elements sputum (163,35.21%), Qixu (92,19.87%), fever (89,19.22%), stasis (65,14.04%), wet (14,3.02%) the main. Syndrome type phlegm retention in the lung (69,19.77%), phlegm lung (43,12.32%), DLS (33,9.46%), lung and kidney deficiency (24,6.88%), phlegm blocking lungs (20,5.73%); The symptoms of COPD in Xinjiang are Slip known for lung (287,61.46%), kidney (142,30.41%), spleen (38,8.14%); disease deficiency (120,16.37%), cold (117,15.96%), Yangxu (109,14.87%), sputum (98,13.37%), Yinxu (90,12.28%).2) Tongue with cchymosis and pale in mainland was higher than in Xinjiang (P<0.01, P<0.05); tongue with purple in Xinjiang was higher than in mainland (P<0.01); constituent ratio of less of body fluid was2.84%in Xinjiang, but in mainland was0.56%, but made no difference; fat tongue, scalloped, purple, green tongue appearance in mainland but not in Xinjiang, yellow fur and greasy fur in mainland was higher than in Xinjiang (P<0.01); and white and thin fur in Xinjiang was high than in mainland (P<0.01); moss, thick fur appearance in mainland but not in Xinjiang, slippery pulse in mainland was higher than in Xinjiang (P<0.01); pulse astringent, tight pulse in Xinjiang were higher than in mainland (P<0.05); floating pulse and veinlets pulse in Xinjiang was higher than in mainland (P<0.01); weakness, soft pulse, intermittent pulse, large pulse just appearance in mailland; slow pulse will only occur in patients in Xinjiang, and accounted for7.93%.4.1) Rats in COPD group, and cold-dry COPD group, we can observed the alveolar fracture fusion, infiltration of inflammatory cells and bronchial smooth muscle thickening, the lung function in cold-dryness COPD group, PEF, Ti, Te, EF50, were higher than them in COPD group, Te and EF50in COPD group were higher than them in control group;2) the body weight, body mass index, and Lee’s index in COPD group and the cold-dryness COPD group were lower than them in control group (P<0.01), and these three parameters in cold-dryness COPD group were lower than them in COPD group (P<0.01, P<0.05, P <0.01). The daily food consumption per lOg body weight in cold-dryness COPD group was greater than it in control group and COPD group;3) Serum IL-1beta in cold-dryness COPD group was higher than that in control group (P<0.05), Serum IL-6, IL-8, TNF-alpha in cold-dryness COPD group were higher than them in control group (P<0.05, P<0.01, P<0.01), and these three parameters in COPD group were also higher than them in control group (P<0.01, P<0.05, P<0.05); the level of IL-10among three groups was not statistically different. The cold-dryness COPD BALF IL-lbeta content was higher than them in control group (P<0.01), IL-6, IL-8, TNF-alpha content in cold-dryness COPD group were higher than them in control group (P<0.01, P<0.01, P<0.01), and they were also higher in COPD group than them in the control group (P<0.05, P<0.05, P<0.05); and IL-6, IL-8was higher in cold-dryness COPD group than them in the COPD group (P <0.05, P<0.05); IL-10among three groups was not statistically different.4) MMP-2 mRNA expression level in cold-dryness COPD and COPD groups were higher than them in control group (P<0.01), and it was higher in cold-dryness COPD group than in the COPD group (P<0.01); MMP-9mRNA expression in both COPD and cold-dryness COPD groups were higher than it in control group (P<0.01), and it was higher in the cold-dryness COPD group than in the COPD group (P<0.05); TIMP-1mRNA expression level of cold dry COPD group and COPD group were higher than it control group (P<0.01); the ratio of MMP-9mRNA/TIMP-1mRNA was highest in cold-dryness COPD group (cold-dryness COPD group>COPD group>control group);5) peripheral blood CD4+in cold-dryness COPD group was lower than it in control group and COPD group (P <0.01); CD8+in cold-drynes COPD and COPD groups were higher than it in control group (P<0.01), while it was higher in cold-dryness COPD group than COPD group (P<0.01); ratio of CD4+/CD8+were lower in cold-dryness COPD and COPD groups (P<0.01), while the it was also lower in cold dry COPD group than in COPD group (P<0.05);6) The AQP-5mRNA of the expression in cold-dryness COPD and COPD groups were lower than it in control group (P<0.01), and it was lower in cold-dryness COPD group than it in the COPD group (P<0.05); MUC5AC expression in cold-dryness COPD and COPD groups were higher than it in control group (P<0.01), and it was higher in cold-dryness COPD group than it in the COPD group (P<0.01); MUC5BmRNA expression in cold-dryness COPD and COPD groups was higher than that in control group (P<0.01), and the cold dry COPD group was higher than the COPD group (P<0.05); ratio of MUC5ACmRNA/MUC5BmRNA was lowest in COPD group (COPD group<the cold dryness COPD group<control group).7) The expression of AQP-4, AQP-5protein in cold dry COPD group were lower than in the COPD group, COPD group was lower than control group; the expression of MUC5AC, MUC5B were highest in cold-dryness COPD group;8) IL-8in lung of rats is closely related to TIMP-1, MMP-2, MUC5B-related the IL-8and MMP-9, MUC5AC. IL-8was negative related to AQP5. IL-10was associated with the expression of MMP-2, MMP-9. IL-10and AQP5were closely negative related to TNF-alpha and MUC5AC; IL-6and TIMP-1, IL-6and AQP5; IL-6and MMP-2, MMP-9, MUC5AC, MUC5B were closely related to TIMP-1and MMP-2; MMP-9; MMP-2and MMP-9, MUC5AC, MUC5B were closely negative related to MMP-2and AQP-5; MMP-9and of MUC5AC, MUC5B were closely related to, MMP-9was negative related to AQP-5; AQP5was negative related to MUC5AC and MUC5B; MUC5AC was correlate with MUC5B. Conclusion:1. We found that the Chinese internal medicine and external application treatment of COPD were effective for COPD, but for different targets, it was complementary advantages combined with Western medicine treatment. Xiaoqinglongtang combined with Western medicine treatment of COPD may, to some extent, improve the clinical efficacy, specifically manifested in increased efficiency and improve PaO2, lower PaCO2, and it also can improve patients’ FEV1. TCM sticking as external treatment combined with medicine should be based on the symptoms of patient. TCM sticking combined with Western medicine can improve the FVC and FEV1. However we did not observe th improvement of FEV1when combined the traditional Chinese medicine with Chinese medicine. TCM sticking combined with TCM improved FEV1/FVC, but there is no synergy with Western medicine.2. We determined that the cold the dry induced and increased the incidence of COPD, which is the one of different characteristics from the COPD in other provinces. When concerned the pattern of syndrome,"cold-dryness" is the special permit and prevalent type of COPD in Xinjiang. When concerned the pathogenesis of the syndrome type, It characterized by " local dry, the whole body cold "and "within the dry, cold outside", when concerned the degree of COPD, cold-dryness is an early COPD syndrome type. Characteristics of COPD in othere provinces were heat, stasis as the phenotypes, deficiency of lung, spleen, kidney is the base; phlegm, blood stasis, virtual throughout the COPD exacerbation and remission of all aspects of the pathogenesis, the major symptoms are cough, sputum, wheezing, shortness of breath, phlegm, blood, qixu. Medicine application in clinical treatment should pay attention to those. Characteristics of COPD in Xinjiang are sputum, cloud, cold, dry as main phenotypes, and deficiency of lung, kidney, spleen as basis, shortness of breath, coughing, wheezing, dry throat, dry mouth, lassitude as main symptoms. Doctors should pay attention to cough expectorant, warm the lung dryness, drug application for qixu.in the clinical treatment of COPD.3. We confirmed that fumes combined with Aikido infusion of elastase for90days can successfully construct the COPD model, and on the basis of which, cold-dry environ-ment can stimulate and establish Xinjiang cold-dryness COPD model. cold-dryness COPD models have some characters such as body weight loss, weight loss, disluster hair color, sputum in airway, decreases in body mass index and Lee’s index, water and food consummation increased, but food utilization is lower; PEF and EF50reduced, Ti and Te value increased. Warm the lung moistening effect of traditional Chinese medicine Cough Powder plus or minus side to improve the certificates of disease symptoms and lung function had a marked effect. But in view of the pathogenesis of the card, when Acrid moist, not too warm and dry to help disability allowance4. To reveal cold dry through the COPD lungs AQP5mRNA and MUC5AC, MUC5BmRNA expression and its corresponding regulation of protein secretion, reducing the water channel protein secretion, increasing mucin secretion, breaking the balance of aquaporin and mucin, thereby all these affect the functional status of the airway mucus, increase the degree of airway obstruction, promote the main pulmonary inflammatory response of the lungs and systemic inflammatory response, disrupt the body’s immune function to cause lung qixu of the body, protection of the lung weakened, aggravate COPD protease-anti-protease imbalance, thus contributing to increased incidence of COPD, may be an important biological basis of cold-dryness COPD. |
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