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1、分類號:R966 密級:UDC: UDC:610 學(xué)校代碼:11065碩士學(xué)位論文明黃湯對 CVA 患者的臨床評價和實驗動物的鎮(zhèn)咳、抗炎和免疫調(diào)節(jié)作用郭昭麗 郭昭麗指 導(dǎo) 教 師 王春波教授 韓彥弢副教授學(xué) 位 類 別 藥學(xué)碩士專 業(yè) 領(lǐng) 域 藥理學(xué)答 辯 日 期 2015.5.252015 年 6 月 5 日Clinical evaluation of Minghuang Decoction on CVA patients and a
2、ssessmentof antitussive, anti-inflammatory and immunomodulation effects inexperimental animal modelAbstractObjective: The aim of this study is to evaluate the therapeutic effects of Minghuang decoction, a traditional Chi
3、nese medicineprescription developed in our hospital by senior traditional Chinese medicine physicians on cough variant asthma (CVA)patients selected according to the cough treatment guideline (2009) by Chinese Medical As
4、sociation. Additional objectivesinclude investigation of the antitussive, anti-inflammatory and immunomodulation effects of Minghuang decoction in mouseand guinea pig model. Methods: For the clinical evaluation, 82 outpa
5、tients who met the diagnosis criteria were randomlyassigned into two groups. Classical treatment group (40 patients) received Salmeterol Xinafoate and Fluticasone Propionatepowder (one dose, b.i.d.). Minghuang decoction
6、group (42 patients) received Minghuang decoction (200 mL, qd). Thetreatment lasted for six weeks. Both group received compound Salbutamol Sulfate aerosol (one press, t.i.d.) until remission.General clinical score was eva
7、luated daily during treatment according to the symptom, and the time point when the scoresignificantly decreased was recorded as cough remission time. Time course changes of the general clinical score at 1, 4 and 6week t
8、reatment were evaluated. The clinical total effective rate after six week treatment was calculated (Sum of the number ofclinical controlled, clinical markedly effective and clinical effective patients divided by the tota
9、l number of treated patients).Spirometer was used to assess lung function before and after treatments. Electronic automatic blood cell counter was used tocount the amount of eosinophil (EOS) in peripheral blood. Serum le
10、vels of IgE, interleukin 13 (IL-13) and interleukin 8 (IL-8)were measured with enzyme-linked immunosorbent assay (ELISA). Hepatic and renal functions were assessed withenzymatic assays. Six months after the treatment, fo
11、llow ups surveyed patients about cough remission time, recurrence rateand common cold incidences. For the animal study, cyclophosphamide (CTX) was used to reproduce immunodeficiencymodel in mouse; 17.5% citric acid solut
12、ion was used to induce cough model in guinea pig, mouse right auricle inflammationmodel was reproduced by applying xylene solution. Experimental design: control group, model group (CTX, citric acid orxylene), Minghuang d
13、ecoction high or low dose groups (24 or 12 g/kg, equavilent to 12 or 6 times of clinical dose,respectively), positive control group (Pidotimod 0.04 g/kg, codeine 0.03 g/kg, or dexamethasone 0.45 mg/kg). Treatmentswere ad
14、ministered via gavage for seven days (immunodeficiency or inflammatory mouse) or three days (cough guinea pig),respectively. For immunodeficiency mouse, phagocytic rate and index for chicken erythrocyte was calculated an
15、d serumhemolysin levels were assessed; for cough guniea pig, cough incubation period and cough time in five minutes were recorded;for auricle inflammation mouse, the auricle swollen degree and inhibition rate were calcul
16、ated. Statistics were performed withSPSS 13.0. Results: The cough remission time of Minghuang decoction was approximately four day. The clinical generalscore improvement was time-dependent. The clinical total effective r
17、ate was 88.1%. Regarding to lung function, the ratio offorced expiratory volume in one second to forced vital capacity (FEV1%) and peak expiratory flow (PEF) significantlyimproved, while the counting of EOS, serum levels
18、 of IgE, IL-13 and IL-8 remarkably decreased (P0.05). Follow up after six months revealed that the average cough remissiontime was about 60 days, recurrence rate and common cold incidences significantly decreased in Ming
19、huang decoction treatedpatients (P<0.05). Animal studies with Minghuang decoction revealed increased phagocytic rate, index and serum hemolysinlevel in immunodeficency mouse as well as decreased auricle swollen degree
20、 and increased swollen inhibition rate in auricleinflammation mouse (P<0.05). In cough guinea pigs, Minghunag decoction significantly prolonged cough incubation periodand decreased cough number (P<0.01). Conclusion
21、s: Minghuang decoction is a reasonable prescription which couldsignificantly improve the clinical symptom and lung function of CVA patients. The mechanism is associated with antitussive,anti-inflammatory (decrease the le
22、vel of inflammatory factors) and immunopotentiation effects.Postgraduate student: Zhao-li Guo (Pharmacology)Directed by Prof. Chun-bo WangAssociate Prof. Yan-tao HanKey Words: Cough variant asthma; Minghuang decoction; a
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